KCNQ1 rs2237895 gene polymorphism increases susceptibility to type 2 diabetes mellitus in Asian populations

BACKGROUND The association of single nucleotide polymorphism of KCNQ1 gene rs2237895 with type 2 diabetes mellitus(T2DM)is currently controversial.It is unknown whether this association can be gene realized across different populations.AIM To determine the association of KCNQ1 rs2237895 with T2DM and provide reliable evidence for genetic susceptibility to T2DM.METHODS We searched PubMed,Embase,Web of Science,Cochrane Library,Medline,Baidu Academic,China National Knowledge Infrastructure,China Biomedical Literature Database,and Wanfang to investigate the association between KCNQ1 gene rs2237895 and the risk of T2DM up to January 12,2022.Review Manager 5.4 was used to analyze the association of the KCNQ1 gene rs2237895 polymorphism with T2DM and to evaluate the publication bias of the selected literature.RESULTS Twelve case–control studies(including 11273 cases and 11654 controls)met our inclusion criteria.In the full population,allelic model[odds ratio(OR):1.19;95%confidence interval(95%CI):1.09–1.29;P<0.0001],recessive model(OR:1.20;95%CI:1.11–1.29;P<0.0001),dominant model(OR:1.27.95%CI:1.14–1.42;P<0.0001),and codominant model(OR:1.36;95%CI:1.15–1.60;P=0.0003)(OR:1.22;95%CI:1.10–1.36;P=0.0002)indicated that the KCNQ1 gene rs2237895 polymorphism was significantly correlated with susceptibility to T2DM.In stratified analysis,this association was confirmed in Asian populations:allelic model(OR:1.25;95%CI:1.13–1.37;P<0.0001),recessive model(OR:1.29;95%CI:1.11–1.49;P=0.0007),dominant model(OR:1.35;95%CI:1.20–1.52;P<0.0001),codominant model(OR:1.49;95%CI:1.22–1.81;P<0.0001)(OR:1.26;95%CI:1.16–1.36;P<0.0001).In non-Asian populations,this association was not significant:Allelic model(OR:1.06,95%CI:0.98–1.14;P=0.12),recessive model(OR:1.04;95%CI:0.75–1.42;P=0.83),dominant model(OR:1.06;95%CI:0.98–1.15;P=0.15),codominant model(OR:1.08;95%CI:0.82–1.42;P=0.60.OR:1.15;95%CI:0.95–1.39;P=0.14).CONCLUSION KCNQ1 gene rs2237895 was significantly associated with susceptibility to T2DM in an Asian population.Carriers of the C allele had a higher risk of T2DM.This association was not significant in non-Asian populations.

Relationship between the rs2241766 ADIPOQ Polymorphism in a Black African Population and the Occurrence of Type 2 Diabetes

Background: Type 2 diabetes mellitus (T2DM) is a metabolic disease, characterized by chronic hyperglycemia. This pathology is linked to various genes whose interaction with the environment promotes its development. The aim of this work was to determine the relationship between the rs2241766 (T/G) polymorphism of the ADIPOQ gene with type 2 diabetes in the black population. Material and Methods: This work was a case-control study, involving type 2 diabetics subjects (n = 94) and controls (n = 82). The study took place from September 2022 to September 2023. Patients were recruited in the Endocrinology Department of the Libreville University Hospital Center. Analysis was performed in the Biochemistry laboratory of the University of Health Sciences in Libreville and at the Research Institute of Health Sciences of Bobodioulasso. Genomic DNA was extracted using the protocol Qiagen kit and the PCR-RFLP method was used to determine the rs2241766 (T/G) polymorphism of the ADIPOQ gene. Results: Only 2 genotypes were found in this population, the TT genotype and the GT genotype. The proportions were not different between the two groups (p = 0.1095) neither the distribution of G and T alleles (p = 0.1095). On the other hand, the HDL hypocholesterolemia was frequent in subjects with the GT genotype compared to TT heterozygous (51.1% vs 48.9%, p = 0.0280;OR = 0.55 [0.30 - 1.01]). Conclusion: There was no association between the rs2241766 (T/G) variant of the ADIPOQ gene and the occurrence of type 2 diabetes in this population. On the other hand, a relationship between HDL hypocholesterolemia and the GT genotype has been established.

Relationship between GCKR gene rs780094 polymorphism and type 2 diabetes with albuminuria

BACKGROUND Diabetic kidney disease is one of the common complications of type 2 diabetes(T2D).There are no typical symptoms in the early stage,and the disease will progress to moderate and late stage when albuminuria reaches a high level.Treatment is difficult and the prognosis is poor.At present,the pathogenesis of diabetic kidney disease is still unclear,and it is believed that it is associated with genetic and environmental factors.AIM To explore the relationship between the glucokinase regulatory protein(GCKR)gene rs780094 polymorphism and T2D with albuminuria.METHODS We selected 252 patients(126 males and 126 females)with T2D admitted to our hospital from January 2020 to October 2020,and 66 healthy people(44 females and 22 males).According to the urinary albumin/creatinine ratio,the subjects were divided into group I(control),group II(T2D with normoalbuminuria),group III(T2D with microalbuminuria),and group IV(T2D with macroalbuminuria).Additionly,the subjects were divided into group M(normal group)or group N(albuminuria group)according to whether they developed albuminuria.We detected the GCKR gene rs780094 polymorphism(C/T)of all subjects,and measured the correlation between GCKR gene rs780094 polymorphism(C/T)and T2D with albuminuria.RESULTS Gene distribution and genotype distribution among groups I-IV accorded with the Hardy-Weinberg equilibrium.Genotype frequency was significantly different among the four groups (P = 0.048, χ^(2)= 7.906). T allele frequency in groups II, III, and IV was significantly higherthan that in group I. Logistic regression analysis of the risk factors for T2D with albuminuria showed that the CT +TT genotype (odds ratio = 1.710, 95% confidence interval: 1.172-2.493) was a risk factor.CONCLUSION CT + TT genotype is a risk factor for T2D with albuminuria. In the future, we can assess the risk of individualscarrying susceptible genes to delay the onset of T2D.

Maternal TMPRSS6 Gene Polymorphism rs855791SNP in Women with Preeclampsia

Introduction: Preeclampsia can lead to several maternal and perinatal adverse effects. There are few published data on the association between transmembrane serine protease 6 (TMPRSS6) gene polymorphism and preeclampsia. Objective: To assess the association between TMPRSS6 gene polymorphism rs855791SNP in women with preeclampsia compared with healthy pregnant women. Method: A case-control study (60 women in each arm) was conducted at Saad Abuaela Maternity Hospital in Khartoum, Sudan. Sociodemographic and clinical data were gathered through a questionnaire. The participant was genotype for TMPRSS6 gene rs855791SNP using Polymerase Chain Reaction and Restriction Fragment Length Polymorphism (PCR-RFLP). The results were confirmed by DNA sequencing. Result: There was no significant difference in the median of age, parity, and body mass index. The distribution of the genotypes and alleles of TMPRSS6 rs855791 was consistent with the HWE. The overall TMPRSS6 rs855791 polymorphism was not significantly associated with preeclampsia. However, the proportion of heterozygotes (TC) was considerably higher in the women with preeclampsia (46.7%) than in the control group (23.3%) (p = 0.001;OR = 2.71;95% CI = 1.21 - 6.07). The proportion of homozygotes (TT) and T alleles was not significantly different between women with preeclampsia and the control group. Conclusion: The overall TMPRSS6 rs855791 polymorphism was not significantly associated with preeclampsia and healthy control.

Genetic polymorphisms in pri-let-7a-2 are associated with ischemic stroke risk in a Chinese Han population from Liaoning, China: a case-control study

Ischemic stroke is a complicated disease, and its pathogenesis has been attributed to the occurrence of genetic polymorphisms.Evidence has suggested that the microRNA let-7a is involved in the pathogenesis of ischemic stroke.Pri-miRNA is the primary transcript, which undergoes several processing steps to generate pre-miRNA and, later, mature miRNAs.In this case-control study, we analyzed the distribution of prilet-7a-2 variants in patients at a high risk for ischemic stroke and the interactions of pri-let-7a-2 variants and environmental factors.Blood samples and clinical information were collected from 1086 patients with ischemic stroke and 836 healthy controls between December 2013 and December 2015 at the First Affiliated Hospital of China Medical University.We found that the rs1143770 CC genotype and the C allele were associated with a decreased risk of ischemic stroke, whereas the rs629367 CC genotype was associated with an increased risk for ischemic stroke.Moreover, these two single-nucleotide polymorphisms were in linkage disequilibrium in this study sample.We analyzed gene-environment interactions and found that rs1143770 exerted a combined effect on the pathogenesis of ischemic stroke, together with alcohol use, smoking, and a history of hypertension.Therefore, the detection of pri-let-7a-2 polymorphisms may increase the awareness of ischemic stroke risk.This study was approved by the Institutional Ethics Committee of the First Affiliated Hospital of China Medical University, China(approval No.2012-38-1) on February 20, 2012, and was registered with the Chinese Clinical Trial Registry(registration number: ChiCTR-COC-17013559) on December 27, 2017.

Single-nucleotide polymorphisms of HLA and Polygonum multiflorum-induced liver injury in the Han Chinese population

BACKGROUND Polygonum multiflorum is one of the leading causes of herb-induced liver injury in China.HLA-B*35:01 is reported to be a potential biomarker of Polygonum multiflorum-induced liver injury(PM-DILI).However,little is known about the relationship between single-nucleotide polymorphisms(SNPs) and PM-DILI.AIM To identify SNPs that indicate susceptibility to PM-DILI METHODS We conducted a systematic study enrolling 382 participants from four independent hospitals,including 73 PM-DILI patients,118 patients with other drug-induced liver injury(other-DILI) and 191 healthy controls.Whole-exome sequencing was performed for 8 PM-DILI patients and 8 healthy controls who were randomly selected from the above subjects.Nineteen SNPs that showed high frequencies in the 8 PM-DILI patients were selected as candidate SNPs and then screened in 65 PM-DILI patients,118 other-DILI patients and 183 healthy controls using the MassARRAY system.HLA-B high-resolution genotyping was performed for the 73 PM-DILI and 118 other-DILI patients.The Han-MHC database was selected as a population control for HLA-B analysis.P <6.25 x 103 after Bolferroni correction was considered significant.RESULTS The frequencies of rslll686806 in the HLA-A gene,rs1055348 in the HLA-B gene,and rs202047044 in the HLA-DRB1 gene were significantly higher in the PM-DILI group than in the control group [27.2% vs 11.6%,P=1.72×105,odds ratio(OR)=3.96,95% confidence interval(Cl):2.21-7.14;42.5% vs 8.6%,P=1.72×10-19 OR=13.62,95% CI:7.16-25.9;22.9% vs 8.1%,P=4.64×106,OR=4.1,95% CI:2.25-7.47].Only rs1055348 showed a significantly higher frequency in the PM-DILI group than in the other-DILI group(42.5% vs 13.6%,P=1.84×10-10,OR=10.06,95% Cl:5.06-20.0),which suggested that it is a specific risk factor for PM-DILI.rs1055348 may become a tag for HLA-B*35:01 with 100% sensitivity and 97.7% specificity in the PM-DILI group and 100% sensitivity and 98.1% specificity in the other-DILI group.Furthermore,HLA-B*35:01 was confirmed to be associated with PM-DILI with a frequency of 41.1% in the PM-DILI group compared with 11.9%(P=4.30×10-11,OR=11.11,95% CI:5.57-22.19) in the other-DILI group and 2.7%(P=6.22×10-166,OR=62.62,95% Cl:35.91-109.20) in the Han-MHC database.CONCLUSION rslll686806,rs1055348,and rs202047044 are associated with PM-DILI,of which,rs1055348 is specific to PM-DILI.As a tag for HLA-B*35:01,rs1055348 may become an alternative predictive biomarker of PM-DILI.

Prevalent false positives of azoospermia factor a （AZFa） microdeletions caused by single-nucleotide polymorphism rs72609647 in the sY84 screening of male infertility

Multiplex polymerase chain reaction （PCR） has been widely used to detect Y-chromosome micredeletions, which is one of the major causes of male infertility. Both the European Academy of Andrology （EAA） and the European Molecular Genetics Quality Network （EMQN） have recommended the use of sY84 and sY86 markers for the detection of azoospermia factor a （AZFa） microdeletion during DNA testing for male infertility. In this study, a large-scale analysis of AZF microdeletion in a total of 630 Chinese males, including healthy semen donors （n=200）, infertile males with normal sperm count （n=226） and patients with either nonobstructive azoospermia or severe oligozoospermia （n=204）, was performed. A series of nine sequence-tagged site （STS） markers from the AZF region of the Y chromosome was used to detect microdeletions. All primers were designed based on the recommendations of the National Center for Biotechnology Information. An unusually high incidence （73/630, 11.6%） of sY84-absent but sY86-present genotypes was observed in the AZFa microdeletion screening. Sequencing the sY84-flanking region revealed a total of 73 patients with sY84-absent but sY86-present genotypes have a T-to-G transversion at the fifth base from the 5＇ end of the reverse sY84 primer. These prevalent false positives, which were not only observed in infertile men, but also observed in donors, resulted from a single-nucleotide polymorphism （SNP） named rs72609647 in the targeting sequence of the reverse sY84 primer. Our study suggests that a pre-screening of existence of rs72609647 polymorphism can prevent the frequent false positive results of AZFa microdeletions detection in the infertile Chinese males. Given the SNP rs72609647 was recently found in a deep sequencing of a Chinese individual, the current EAA and EMQN standards may need to be scrutinized among different populations to avoid the potential genetic variations in the primer binding sequences.

Apolipoprotein E polymorphisms increase the risk of post-stroke depression

Recent reports have shown that apolipoprotein E （APOE） polymorphisms are involved in neurodegenerative disease. However, it is unclear whether APOE affects post-stroke depression. Accordingly, we hypothesized that APOE polymorphisms modify the risk of post-stroke depression. Here, we performed a hospital-based case-control study （including 76 cerebral infarction cases with post-stroke depression, 88 cerebral infarction cases without post-stroke depression, and 109 controls without any evidence of post-stroke depression or cerebral infarction） to determine possible association between APOE rs429358 and rs7412 polymorphisms and risk of post-stroke depression. Our findings show no difference among the groups with regards genotype distribution of the rs7412 polymorphism. In contrast, APOE genotypes with rs429358-C alleles increased the risk of post-stroke depression. Further, the rs429358 polymorphism was associated with significantly decreased regional cerebral blood flow values in the left temporal lobe of post-stroke depression cases. Additionally, the rs429358 polymorphism was not only associated with depression severity, but with increasing serum levels of total cholesterol. These resuits suggest that the APOE rs429358 polymorphism is associated with increased risk of developing post-stroke depression, and that APOE rs429358-C allele genotypes may be detrimental to recovery of nerve function after stoke. Indeed, these findings provide clinical data for future post-stroke depression gene interventions.

Meta- analysis of association between K469E polymorphism of the ICAM-1 gene and retinopathy in type 2 diabetes

AIM: To collectively evaluate the association of intercellular adhesion molecule-1(ICAM-1) gene K469 E polymorphism(rs5498) with diabetic retinopathy(DR) in patients with type 2 diabetic mellitus(T2DM). METHODS: Overall review of available literatures relating K469 E polymorphism to the risk of DR was conducted on 4 electronic databases. Meta-analysis was performed by Stata 12.0 to calculate pooled odds ratios(ORs). Potential sources of heterogeneity and bias were explored.RESULTS: Seven studies with genotype frequency data including 1120 cases with DR and 956 diabetic controls free of DR were included. Meta-analysis did not show significant association of K469 E polymorphism with DR(P 】0.05). A statistically significant association was detected between the K469 E polymorphism and proliferative DR(PDR) in Asians only in dominant model(GG+AG vs AA) with pooled OR of 0.729(95%CI: 0.564-0.942, P=0.016, P heterogeneity=0.143), however, this association was not detected in recessive model(AG +AA vs GG;OR=1.178, 95%CI: 0.898-1.545, P =0.236, P heterogeneity=0.248)or allelic model(G vs A; OR=0.769, 95% CI: 0.576-1.026,P =0.074, P heterogeneity=0.094). No publication bias was found by Funnel plot, Begg’s and Egger’s test. CONCLUSION: This research found no statistically significant association between ICAM-1 gene K469 E polymorphism and DR in patients with T2 DM, but showed significant association of the K469 E polymorphism with PDR in Asian diabetic patients only in dominant model. Further investigation would be required to consolidate the conclusion.

PPARGC1A rs8192678 G>A polymorphism affects the severity of hepatic histological features and nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease

BACKGROUND The association between PPARGC1A rs8192678 and nonalcoholic fatty liver disease(NAFLD)requires further confirmation.In addition,it is still unknown whether PPARGC1A rs8192678 is associated with hepatic histological features in NAFLD in the Chinese population.AIM To investigate the interaction between PPARGC1A rs8192678 and nonalcoholic steatohepatitis(NASH),and whether this polymorphism is associated with hepatic histological features.METHODS Fifty-nine patients with liver biopsy-proven NAFLD and 93 healthy controls were recruited to a cohort representing the Chinese Han population.The SAF(steatosis,activity,and fibrosis)scoring system was used for hepatic histopathological evaluation.The polymorphisms of PPARGC1A rs8192678 and patatin-like phospholipase domain-containing protein 3(PNPLA3)rs738409 were genotyped.The intrahepatic mRNA expression of PPARGC1A was evaluated by real-time polymerase chain reaction.RESULTS Thirty-seven patients with NAFLD had NASH,of which 12 were nonobese.The PPARGC1A rs8192678 risk A allele(carrying GA and AA genotypes)had the lowest P value in the dominant model;the odds ratio(OR)for NAFLD was 2.321[95%confidence interval(CI):1.121-4.806].After adjusting for age,sex,and the PNPLA3 rs738409 risk G allele,the PPARGC1A rs8192678 A allele was a risk factor for NAFLD(OR 2.202,95%CI:1.030-4.705,P=0.042).The genetic analysis showed that patients with NAFLD,moderate-to-severe steatosis(S2-3),and Activity 2-4(A≥2)were more likely to carry A in PPARGC1A rs8192678(OR 5.000,95%CI:1.343-18.620,P=0.012;and OR 4.071,95%CI:1.076-15.402,P=0.031).The multivariate logistic regression analysis showed that PPARGC1A rs8192678 risk A allele was also independently associated with S2-3,A≥2,and NASH(OR 6.190,95%CI:1.508-25.410,P=0.011;OR 4.506,95%CI 1.070-18.978,P=0.040;and OR 6.337,95%CI:1.135-35.392,P=0.035,respectively)after adjusting for age,sex,body mass index,and PNPLA3 rs738409 risk G allele.The results also showed that this polymorphism was associated with nonobese NASH(OR 22.000,95%CI:1.540-314.292,P=0.021).The intrahepatic expression of PPARGC1A mRNA was significantly lower in the group of patients who carried the risk A allele(P=0.014).CONCLUSION The PPARGC1A rs8192678 risk A allele is associated with NAFLD,and with S2-3,A≥2 and NASH in NAFLD patients,independent of PNPLA3 rs738409,and may be associated with nonobese NASH.

Association between interleukin-21 gene rs907715 polymorphism and gastric precancerous lesions in a Chinese population

BACKGROUND The single nucleotide polymorphisms of interleukin-21(IL-21)gene were confirmed to be related to various diseases,but no studies have examined the possible role of IL-21 single nucleotide polymorphisms(SNPs)(rs907715,rs2221903,and rs12508721)in gastric precancerous lesions.AIM To explore the associations between SNPs of IL-21 gene(rs907715,rs2221903,and rs12508721)and gastric precancerous lesions in a Chinese population.METHODS Three SNPs of IL-21 were genotyped using polymerase chain reaction–ligase detection reaction in 588 cases and 290 healthy controls from May 2013 to December 2016 in northwestern China.Gastric precancerous lesions were confirmed by endoscopic examination and categorized as non-atrophic gastritis,atrophic gastritis,and intestinal metaplasia.Descriptive statistic and logistic regression were used for data analyses.RESULTS IL-21 rs907715 genotype CC and C frequencies were higher in in patients with gastric precancerous lesions than in the controls(OR=1.59,95%CI:1.06-2.38,P=0.013;OR=1.28,95%CI:1.01-2.22,P=0.044,respectively)after adjusting for confounding factors.For SNP rs907715 in intestinal metaplasia patients,significant differences between cases and controls were observed in the frequencies of genotype CC and C(OR=1.92,95%CI:1.24-2.98,P=0.004;OR=1.53,95%CI:1.04-2.24,P=0.028,respectively);for non-atrophic gastritis and atrophic gastritis patients,the CC and C genotypes showed no significant association with risk in all models.No association between either rs2221903 or rs12508721 and gastric precancerous lesions was found in the present study.In the haplotype analysis,the TC haplotype(rs907715 and rs12508721)and TT haplotype(rs2221903 and rs907715)were more frequent in the case group than control group(P<0.05).CONCLUSION Our findings indicate that SNP rs907715 of IL-21 gene is associated with gastric precancerous lesions.The TC haplotype(rs907715 and rs12508721)and TT haplotype(rs2221903 and rs907715)increased the risk of gastric precancerous lesions.If confirmed,these findings will shed light on the etiology of precancerous lesions.

Genetic association of rs7754840 and rs7756992 polymorphisms in the CDKAL1 gene and gestational diabetes mellitus in selected Filipino pregnant women

Objective:To investigate the possible association between rs7754840 and rs7756992 polymorphisms of CDKAL1 gene and susceptibility to gestational diabetes mellitus(GDM)in a Filipino pregnant population.Methods:A total of 101 patients with GDM and 99 women without GDM were included.Two CDKAL1 gene single nucleotide polymorphisms(SNPs),namely rs7754840 and rs7756992,were genotyped by using TaqMan allelic discrimination assays.Mann-Whitney U test,median and interquartile range were used to describe physical and biochemical characteristics.The differences in the genotype and allele distribution of the target genetic variants among the two groups of participants were assessed by using Chi-square test.Conformity to Hardy-Weinberg equilibrium was tested prior to conducting further analysis.Multiple logistic regression model was used to investigate the effects of the genotype models on GDM development.Results:There was no observed correlation between the genotypes of the rs7754840 SNP and oral glucose tolerance test parameters.Consequently,there was no significant association between genetic models of the rs7754840 SNP and GDM risk(additive OR 1.43,95%CI 0.82-2.50,P=0.21;dominant OR 1.21,95%CI 0.57-2.59,P=0.62;recessive OR 1.63,95%CI 0.86-3.09,P=0.13).Conclusions:The results of this study suggest no association between CDKAL1 gene variant rs7754840 and GDM development in Filipino pregnant women.Further studies with a larger population should be performed to validate our findings.

A polymorphism within ErbB4 is associated with risk for hepatocellular carcinoma in Chinese population

AIM:To investigate the association between hepatocel-lular carcinoma (HCC) susceptibility and a 12-bp inser-tion/deletion polymorphism (rs6147150) in the 3'UTR of ErbB4.METHODS:Using a case-control design,the rs6147150 genotypes in 270 patients with HCC and 270 healthy controls were determined by direct polymerase chain reaction and polyacrylamide gel electrophoresis.Logistic regression was used to analyze the association between the polymorphism and cancer risk.RESULTS:Computational modeling suggested that rs6147150 was located in the seed region of hsa-let-7c,a potential target sequence in ErbB4 3'UTR.Logistic re-gression analysis showed that,compared with individu-als homozygous for wild-type,heterozygotes [adjusted odds ratio (OR)=1.48,95% confidence interval (CI)= 1.03-2.17,P=0.034] and individuals homozygous for 12-bp del/del (OR=2.50,95% CI=1.37-4.56,P=0.001) were at significantly higher risk of HCC.Car-riers of the "del" allele of rs6147150 had a 1.59-fold increased risk for HCC (95% CI=1.22-2.07,P=0.003).CONCLUSION:rs6147150 may be associated with HCC risk,in part through let-7c-mediated regulation,and may be involved in the pathogenesis of HCC in Chi-nese populations.

Associations of IFN-γ rs2430561 T/A,IL28B rs12979860 C/T and ERα rs2077647 T/C polymorphisms with outcomes of hepatitis B virus infection:a meta-analysis

Several studies investigated associations of IFN-γ rs2430561 T/A,IL28 B rs12979860 C/T and ERα rs2077647 T/C gene polymorphisms with outcomes of hepatitis B virus（HBV） infection,but the results were controversial.Therefore,we performed a meta-analysis of all published observational studies to address this inconsistency.Literature was searched in online database and a systematic review was conducted based on the search results.A total of 24 studies were included and dichotomous data were presented as odds ratio（OR） with a 95%confidence interval（CI）.The rs2430561 T allele was associated with reduced persistent HBV infection risk（T vs.A：OR,0.690;95%CI,[0.490,0.971]）,while the rs2077647 T allele significantly increased the risk of persistent HBV infection（T vs.C：OR.1.678;95%CI,[1.212,2.3231）.Rs 2077647 CC might play a role in protecting individuals against HBV persistence（TT vs.CC：OR,4.109;95%CI,[2.609,6.473]）.Furthermore,carriers of the rs2430561 TT genotype were more likely to clear HBV spontaneously compared with those of the AA genotype（TT vs.AA：OR,0.555;95%CI,[0.359,0.856]）.For rs12979860 C/T polymorphism,no significant correlation with HBV infection outcomes was found.In subgroup analyses,the results were similar to those of overall analysis.However,for rs2077647 TT vs.TC＋CC,significantly increased risks were observed in the Asian and hospital-based population,but not in the overall analysis.IFN-γrs2430561 T/A and ERα rs2077647 T/C genetic polymorphisms were associated with outcomes of HBV infection,but no association was found between IL28 B rs12979860 C/T and HBV infection.

Association between homeobox protein transcript antisense intergenic ribonucleic acid genetic polymorphisms and cholangiocarcinoma

BACKGROUND Cholangiocarcinoma(CCA)represents a rare but highly aggressive malignancy that is often challenging to diagnose,especially in early stages.The role of existing tumor biomarkers for CCA diagnosis,remains controversial due to their low sensitivity and specificity.Increasing evidence has implicated long non-coding ribonucleic acid polymorphisms with cancer susceptibility in a variety of tumor types.The association between long non-coding ribonucleic acid homeobox protein transcript antisense intergenic ribonucleic acid(HOTAIR)polymorphisms and CCA risk has not been reported yet.AIM To investigate the influence of HOTAIR variants on the risk of CCA development.METHODS We conducted a case-control study in which three HOTAIR single nucleotide polymorphisms(rs920778,rs4759314 and rs7958904)were genotyped in a Greek cohort.Our study population included 122 CCA patients(80 males and 42 females)and 165 healthy controls.The polymorphisms under investigation were examined in peripheral blood samples.RESULTS HOTAIR rs4759314 AG and GG genotypes were associated with a significantly increased CCA risk[P=0.004,odds ratio:3.13;95%confidence interval:1.65-5.91 and P=0.005,odds ratio:12.31;95%confidence interval:1.48-101.87,respectively].However,no significant associations of HOTAIR rs920778,and rs7958904 were detected.Similarly,we found no significant associations between rs4759314 AA genotype and CCA susceptibility.CONCLUSION HOTAIR rs4759314 AG and GG genotypes may be implicated with CCA development and may serve as a potential diagnostic biomarker.

PNPLA3 polymorphism increases risk for and severity of chronic hepatitis C liver disease

AIM To examine the association of PNPLA3 polymorphisms in chronic hepatitis C patients and development of liver disease spectrum. METHODS Literature was searched systematically from Pub Med/MEDLINE, EMBASE, and Cochrane search engines for full-length articles written in English that examined PNPLA3 polymorphism in chronic hepatitis C(CHC) patients. Studies evaluating the association of PNPLA3 polymorphism spectrum(fatty liver, steatohepatitis, cirrhosis, and hepatocellular carcinoma) of CHC were included. Pooled data are reported as OR with 95%CI. Our study endpoint was the risk of the entire liver disease spectrum including: Steatosis/fatty liver, cirrhosis, and hepatocellular carcinoma in CHC patients with PNPLA3 polymorphisms.RESULTS Of 380 studies identified, a total of 53 studies were included for full-text review. Nineteen on chronic he-patitis C were eligible for analysis. Pooled ORs for rs738409 GG compared to CC and CG among patients with fatty liver was 2.214(95%CI: 1.719-2.853). ORs among advanced fibrosis/cirrhosis were 1.762(95%CI: 1.258-2.468). Similar odds ratios among hepatocellular carcinoma patients were 2.002(95%CI: 1.519-2.639). Pooled ORs for rs738409 GG and CG compared to CC among patients with fatty liver were 1.750(95%CI: 1.542-1.986). Pooled ORs for advanced fibrosis/cirrhosis patients were 1.613(95%CI: 1.211-2.147). All analyses were homogenous and without publication bias except one. The associations were maintained after adjusting for publication bias and heterogeneity. CONCLUSION PNPLA3 polymorphisms have strong association with increased risk and severity of the liver disease spectrum in CHC patients.

No association between a polymorphism of the adenylate cyclase type IX gene and major depressive disorder in the Chinese Han population

Previous studies have demonstrated that a missense single-nucleotide polymorphism variant （2316A〉G;rs2230739）of the adenylate cyclase type IX gene was associated with bipolar disorder and affective disorder.We determined genotype and allele frequencies using a ligase detection reaction method in 315 patients with major depressive disorder and 278 unrelated, sex-matched healthy control subjects.We did not detect any statistically significant differences in genotype and allele frequencies between patients and healthy control subjects.Furthermore,we found no significant difference between genders in major depressive disorder,nor between patients and controls in the same gender.These results suggest that 2316A〉G（rs2230739）may not be a risk factor for increasing susceptibility to major depressive disorder in the Chinese Han population.

Investigation of FOXP3 (rs3761548) polymorphism with the risk of preeclampsia and recurrent spontaneous abortion: A systemic review and meta-analysis

Objective:To investigate the association between forkhead box P3(FOXP3)(rs3761548)polymorphism and the risk of preeclampsia and recurrent spontaneous abortion.Methods:Literature on the association of FOXP3 gene polymorphisms and susceptibility to preeclampsia and unexplained recurrent spontaneous abortion was retrieved by searching databases such as PubMed,Science Direct,Google Scholar and Embase from 2000 to 2021.The association measure was analyzed using an odds ratio(OR)and 95%confidence interval(CI).All the statistical analyses were executed using RevMan 5.4 software.Results:In the present meta-analysis,11 articles were analyzed.The pooled results showed no association between FOXP3 gene polymorphism(rs3761548)and preeclampsia risk in allelic,recessive,dominant and over dominant contrast models.FOXP3 gene polymorphism(rs3761548)showed an association with recurrent abortion in allelic,recessive and dominant models(OR 1.85,CI 1.59-2.14;OR 2.02,95%CI 1.56-2.62;OR 2.69,95%CI 1.50-4.83,respectively),while no association in the over dominant contrast model(OR 1.35,CI 0.87-2.10).Conclusions:In the present study,FOXP3 gene(rs3761548)polymorphism is associated with risk of recurrent spontaneous abortion but not preeclampsia.However,larger sample size and multiracial studies are needed in the future to confirm the findings.

ABCB9 polymorphism rs61955196 is associated with schizophrenia in a Chinese Han population

BACKGROUND Schizophrenia(SCZ)is a complex disease which can be affected by both genetic and environmental factors.Prenatal famine exposure may cause changes in DNA methylation levels of genes.Meanwhile,maternal nutrition during pregnancy is a pivotal environmental factor in the development of SCZ.DNA methylation may be an intermediate factor mediating exposure to famine during pregnancy and SCZ,and DNA methylation quantitative trait loci might serve as a promising tool for linking SCZ and prenatal famine.AIM To analyze the association between prenatal famine exposure and SCZ risk in Northeast Han Chinese through analysis of DNA methylation related loci.METHODS A total of 954 Han Chinese from Northeast China were recruited,including 443 patients with SCZ and 511 healthy controls.The participants were further divided into famine(born in 1960-1962)and non-famine(born in 1963-1965)groups to investigate the effect of prenatal famine exposure.Four single-nucleotide polymorphisms(SNPs)selected according to the relevant literature were genotyped,namely,rs11917047 in PTPRG,rs2239681 in IGF2,rs3842756 in INSIGF,and rs61955196 in ABCB9.DNA were extracted from peripheral blood samples,and the genotypes of these SNP loci were detected using the improved Multiple Ligase Detection Reaction multiple SNP typing technique.The associations of the DNA methylation related SNPs with SCZ risk and prenatal famine,and their interactions were analyzed using logistic regression analysis and generalized multifactor dimensionality reduction(GMDR)software.RESULTS Based on the sequencing data,genotype distributions and allele frequencies of the four selected SNPs were determined.All genotype frequencies of the four SNPs in the healthy control group were tested for deviation from Hardy-Weinberg equilibrium(P>0.05).Logistic regression analysis showed that rs61955196 was significantly associated with SCZ risk in the log-additive model[odds ratio(OR):1.22;95%confidence interval(CI):1.01-1.48;P=0.040].We also found that the rs61955196 allele was related with an enhanced risk of SCZ(G>C,OR:1.22;95%CI:1.01-1.47;P=0.042).However,no associations were observed between rs11917047,rs2239681,or rs3842756 and SCZ risk.Under the optimal genetic model,no significant association of famine with the four SNPs was seen.Though the gene–gene interactions between rs2239681 and rs61955196 were found in GMDR analysis,none of the gene-gene interactions and gene-famine interactions were associated with the risk of SCZ.CONCLUSION Our study suggested that rs61955196 in ABCB9 is associated with SCZ susceptibility in Northeast Han Chinese,providing insight into genetic effects on SCZ.

The -250G>A polymorphism in the hepatic lipase gene promoter influences plasma lipid profile and lipoprotein ratio in patients with ischemic stroke

Objective:To evaluate the influence of–250G>A(rs2070895)polymorphism in hepatic lipase gene(LIPC)promoter on plasma lipid parameters of ischemic stroke patients.Methods:A total of 100 stroke patients and 100 control subjects matched for sex(59 men and 41 women)and age were selected.Hepatic lipase activity and lipid profiles were measured while lipoprotein ratios were calculated.Genotyping of the–250G>A promoter polymorphism of the LIPC was performed by the polymerase chain reaction and restriction fragment length polymorphism method combined with 2%gel electrophoresis and then confirmed by direct sequencing.The LIPC promoter gene sequencing data were compared with refseqNG011465.1 LIPC from GenBank.Results:The frequencies of GG,GA and AA genotypes of LIPC rs2070895 polymorphism were 39%,45%and 16%for the control,10%,37%and 53%for the stroke subjects(P<0.0001),respectively.The frequencies of G and A alleles were 61.5%and 38.5%for the control,and 28.5%and 71.5%for the stroke subjects(P<0.0001).Our study shows that the mutant allele of the LIPC promoter was associated with dyslipidemia,lower hepatic lipase activity,and this variation contributed to the increased defective plasma high-density lipoprotein-cholesterol(HDL-C),HDL2-C and HDL3-C concentration for both subjects.The control subjects had 6 single nucleotide polymorphism and 6 amino acid substitutions while the stroke subjects had 32 single nucleotide polymorphism and 20 amino acid substitutions.Conclusions:LIPC–250G>A polymorphism can influence plasma lipid profiles and lipoprotein ratios in patients with ischemic stroke.