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.

Association between Gene Polymorphisms and SNP-SNP Interactions of the Matrix Metalloproteinase 2 Signaling Pathway and the Risk of Vascular Senescence

Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS).Methods In this cross-sectional study,between May and November 2022,peripheral venous blood of151 VS patients(case group)and 233 volunteers(control group)were collected.Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway,assessed through carotid-femoral pulse wave velocity(cf PWV),and analyzed using multivariate logistic regression.The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction(MDR)and generalized multifactor dimensionality regression(GMDR)modeling.Results Within the multivariate logistic regression models,four SNPs were screened to have significant associations with VS:chemokine(C-C motif)ligand 2(CCL2)rs4586,MMP2 rs14070,MMP2rs7201,and MMP2 rs1053605.Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype,and those of the T/T genotype had a19.375-fold increased risk.CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions.Conclusion CCL2 rs4586,MMP-2 rs14070,MMP-2 rs7201,and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.

AAV2-PDE6B restores retinal structure and function in the retinal degeneration 10 mouse model of retinitis pigmentosa by promoting phototransduction and inhibiting apoptosis

Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.

Polymorphism of Intron 14 of Porcine CACNA2D1 Gene and Effects on Muscular pH_(45)

[ Objective] To detect polymorphism of intron 14 of porcine CACNA2Dt gene and thus provide conditions for the marker-assisted selec- tion of pork quality traits. [Method] The polymorphism of the exon 14 and intron 14 of porcine CACNA2D1 gene was detected in six breeds by PCR- SSCP. The genetic effects of different genotypes on the pH45 value of eye muscle and ham joint muscle were also analyzed. I-Result] There were three kinds of genotypes, namely, AA, AG and GG, in the intron 14 of porcine CACNA2 DI gene. The polymorphic locus （ G --~ A） was at the 1 145 nt of the sequence （GenBank Accepted No. FJ156361 ）. The results of X2 test showed that the distribution of these three kinds of genotypes was significantly different in the six breeds （P〈0.05）. The pH45 values of eye muscle and ham joint muscle were significantly different between geno- type AA and genotype AG of pigs in F2 generation from the Jianhua x Pietrain resource family （ P 〈 0.05）. [Conclusion ] The polymorphism of the in- tron 14 of porcine CACNA2D1 gene has effects on the pH45 values of eye muscle and ham joint muscle.

Evaluating the scope of human leukocyte antigen polymorphisms influencing hepatitis B virus-related liver cancer and cirrhosis through multi-clustering analysis

Hepatitis B virus remains a major cause of cirrhosis and hepatocellular carcinoma,with genetic polymorphisms and mutations influencing immune responses and disease progression.Nguyen et al present novel findings on specific human leukocyte antigen(HLA)alleles,including rs2856718 of HLA-DQ and rs3077 and rs9277535 of HLA-DP,which may predispose individuals to cirrhosis and liver cancer,based on multi-clustering analysis.Here,we discuss the feasibility of this approach and identify key areas for further investigation,aiming to offer insights for advancing clinical practice and research in liver disease and related cancers.

Evaluation of angiotensin converting enzyme insertion/deletion, alpha adducin (ADD1) G460W, and IL-10 gene polymorphisms, and determination of prognostic effects in idiopathic sudden sensorineural hearing loss

Objective:The aim of this study was to examine angiotensin converting enzyme(ACE)insertion/deletion,alpha adducin,and interleukin-10(IL-10)gene polymorphisms(GPs)in terms of both idiopathic sudden sensorineural hearing loss(ISSNHL)risk and their potential prognostic effects.Methods:The study group consisted of 70 patients and the control group consisted of 50 patients.Venous blood samples were analyzed for relevant GPs via kompetitive allele-specific polymerase chain reaction.Age,sex,affected side,tinnitus,and vertiginous symptom status,number of days between symptom onset and hospital admission,pure tone audiometry results at admission and after treatment were included in the study.Data were compared statistically.Results:The D allele of ACE insertion/deletion GP was significantly more frequent in patients with ISSNHL than in the control group(p=0.032).II genotype was associated with a reduced risk of ISSNHL(p=0.036).The amount of hearing loss was significantly higher in patients with the TT genotype(p=0.027)and T allele of the IL-10 GP(p=0.035)than in the patients without this allele.Severe hearing loss was a poor prognostic factor(p=0.008).Conclusions:The D allele of ACE insertion/deletion GP may be involved in the ISSNHL etiology.Due to the association of this allele with occlusive vascular pathologies,ischemia is believed to be a common pathway in the etiopathogenesis of ISSNHL.

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.

Distribution of gene polymorphisms associated with aspirin antiplatelet in the Han NSTEMI population

Objective:To analyze the genotype and allele distribution characteristics of GPⅢa PLA2(rs5918),PEAR1(rs12041331),and PTGS1(rs10306114)genes related to the antiplatelet pharmacological effects of aspirin,providing reference for individualized treatment of Chinese Han NSTEMI patients.Methods:A total of 107 Han patients with NSTEMI in Beijing Luhe Hospital affiliated to Capital Medical University from January 2016 to December 2022 were selected as the research subjects.The genotypes of GPⅢa PLA2(rs5918),PEAR1(rs12041331)and PTGS1(rs10306114)were detected by fluorescence staining in situ hybridization.The frequency distribution and allele distribution of genotype were analyzed.The results were analyzed whether there were statistical differences in the distribution of related alleles between the Han NSTEMI population and some populations in the 1000 Genomes database.Results:In the Han NSTEMI population,the genotype frequencies of GPⅢa PLA2(rs5918)locus were TT 97.20%,TC 2.80%and CC 0%,the allele frequencies were T 98.60%and C 1.40%.The genotype frequencies of PEAR1(rs12041331)locus were GG 42.06%,GA 44.86%and AA 13.08%,the allele frequencies were G 64.49%and A 35.51%.The genotypes at the PTGS1(rs10306114)locus were all AA(100%),no AG or GG genotype was found.Conclusion:In the NSTEMI population of Han nationality,the mutation at GPⅢa PLA2(rs5918)site related to aspirin antiplatelet pharmacology is rare,and there is no mutation at PTGS1(rs10306114)site.Wild homozygotes are dominant in these two gene loci,while mutations in PEAR1(rs12041331)are more common.Some of the findings in this study are similar to those in previous reports or other populations included in the relevant database;however,some results differ from previous reports or other populations。

AGTR1 A1166C gene polymorphism is associated with the effectiveness of valsartan monotherapy in Chinese patients with essential hypertension:A retrospective analysis

Objective:To investigate whether angiotensinⅡtype 1 receptor(AGTR1 A1166C)gene polymorphism was associated with the effectiveness of valsartan monotherapy in Chinese patients with essential hypertension.Methods:This retrospective analysis included 198 patients(≥18 years of age)who received valsartan monotherapy(80 mg/day)for newly developed essential hypertension at the authors’center between January 1,2020 and December 31,2023.Genotyping for AGTR1 A1166C gene polymorphism was done by polymerase chain reaction(PCR)-melting curve analysis of genomic DNA from peripheral blood samples.A dominant genetic model for AGTR1 A1166C(AA genotype versus AC+CC genotype)was used.Multivariate regression analysis of baseline variables and AGTR1 polymorphism was conducted to identify predictors of target blood pressure attainment(<140/90 mmHg)at the 4-week follow-up.Results:The median age of the 198 patients was(53.7±13.5)years,and 58%were men.Genotyping assays showed that 164 patients had the AA genotype,and 34 patients were of the AC/CC genotype,including 30 with the AC genotype and 4 with the CC genotype.Allele distribution was consistent with Hardy Weinberg equilibrium.109 Patients(55.1%)attained the blood pressure target.Multivariate analysis showed that smoking(versus no smoking,HR 0.314,95%CI 0.159-0.619,P=0.001)and AGTR1 A1166C AA genotype(versus AC/CC,HR 2.927,95%CI 1.296-6.611,P=0.023)were significant and independent predictors of target attainment.25 Patients(73.5%)with AGTR1 A1166C AC/CC genotype attained the target versus 51.2%(51/164)of patients with AGTR1 A1166C AA genotype(P=0.017).Patients with AGTR1 A1166C AC/CC genotype had a significantly greater reduction in systolic blood pressure[(33.1±10.8)mmHg versus(29.2±11.7)mmHg in AA carriers;(P=0.029)].Conclusions:Hypertensive patients carrying one or two C alleles of the AGTR1 A1166C gene were more responsive to valsartan treatment.

Association between 5-HTR1A gene C-1019G polymorphism and antidepressant response in patients with major depressive disorder:A meta-analysis

BACKGROUND Major depressive disorder(MDD)is a substantial global health concern,and its treatment is complicated by the variability in individual response to antide-pressants.AIM To consolidate research and clarify the impact of genetic variation on MDD treatment outcomes.METHODS Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines,a systematic search across PubMed,EMBASE,Web of Science,and the Cochrane Library was conducted without date restrictions,utilizing key terms related to MDD,serotonin 1A receptor polymorphism(5-HTR1A),C-1019G polymorphism,and antidepressant response.Studies meeting inclusion criteria were thoroughly screened,and quality assessed using the Newcastle-Ottawa Scale.Statistical analyses,includingχ2 and I²values,were used to evaluate heterogeneity and fixed-effect or random-effect models were applied accordingly.RESULTS The initial search yielded 1216 articles,with 11 studies meeting criteria for inclusion.Analysis of various genetic models showed no significant association between the 5-HTR1A C-1019G polymorphism and antidepressant efficacy.The heterogeneity was low to moderate,and no publication bias was detected through funnel plot symmetry and Egger's and Begg's tests.CONCLUSION This meta-analysis does not support a significant association between the 5-HTR1A C-1019G polymorphism and the efficacy of antidepressant treatment in MDD.The findings call for further research with larger cohorts to substantiate these results and enhance the understanding of antidepressant pharmacogenetics.

Toll-like receptors 2 polymorphism is associated with psoriasis: A case-control study in the northern Chinese population

Background:Psoriasis is a disease caused by genetics and immune system dysfunction,affecting the skin and joints.Toll-like receptors(TLRs)play an important role in triggering the innate immune response and controlling adaptive immunity.The role of TLR2 in the progression of psoriasis is not well understood.Methods:A case-control study was conducted on a northern Chinese Han population,consisting of psoriasis patients and healthy control subjects.Genotyping was performed using the tetra-primer amplification refractory mutation system-polymerase chain reaction(ARMS-PCR),and allele and genotype frequencies of four SNPs in TLR2 were analyzed in 270 psoriasis patients and 246 healthy controls.Results:Four TLR2 SNPs(rs11938228,rs4696480,rs3804099,rs5743699)were genotyped and found to be in linkage disequilibrium.The genotype distributions of rs11938228 and rs4696480 in two groups were in Hardy-Weinberg equilibrium and statistically significant except for the overdominance model.The haplotypes ATTC and ATCC were found to be protective against psoriasis.Conclusion:Our study found a correlation between TLR2 genetic variations and the likelihood of psoriasis in northern China.

Polymorphism of p16INK4a gene and rare mutation of p15INK4b gene exon2 in primary hepatocarcinoma

INTRODUCTION Hepatocellular carcinoma(HCC)is the mostcommon cause of death from cancer in China.Themechanisms of hepatocarcinogenesis are not yetknown clearly,p16INK4a gene,the multiple tumorsuppressor gene 1(MTS1),encodes P16 protein,which acts as an inhibitor by binding directly toCDK4 and CDK6 and preventing its association

Job Stress, Gene Polymorphism of β_2-AR, and Prevalence of Hypertension

Objective To study the interactive effect of job stress and genetic susceptibility （or gene polymorphism） on hypertension. Methods A cross-sectional epidemiological study was conducted in 452 workers from a thermal power plant in China. Extrinsic effort, occupational reward, and over-commitment were measured. Hypertensive patients were defined by three phases of screening, reexamination, and final diagnosis. β2-AR genotypes and allele frequencies at amino acid positions 16 （β2-AR-16： Arg→Gly） and 27 （β2-AR-27： Gln→Glu） were identified by PCR-RFLE Results Job stress was related with the prevalence of hypertension in males （P〈0.05）, whereas no significant relationship was found in females （P〉0.05）. Differences in genotypes and allele frequencies of the β2-AR-16 were statistically significant between the hypertension and control groups （P〈0.05）, whereas those of β2-AR-27 were not （P〉0.05）. The prevalence of hypertension was higher in individuals carrying Gly16 allele than in those carrying Arg16 allele of the high job stress group （P〈0.01 or 0.05）. Conclusion High job stress and polymorphism of β2-AR-16 have an interactive effect on the prevalence of hypertension in male workers.

Polymorphism of N-acetyltransferase 2 (NAT2) Gene Polymorphism in Shanghai population: Occupational and Non-occupational Bladder Cancer Patient Groups

Objective Arylamine N-acetyltransferases (NATs) are involved in the detoxification of aromatic amines and hydrazine. In order to explore the possible association of NAT2 polymorphism with bladder cancer risk in benzidine exposed or non-exposed Chinese individuals, healthy subjects, subjects with bladder cancer of a former benzidine exposed cohort in Shanghai dyestuff industry and a group of bladder cancer patients without known occupational exposure to aromatic amines were genotyped for NAT2 gene polymorphism. Methods NAT2 genotyping was performed with a set of RFLP procedures at seven major polymorphic loci of gene coding area: G191A, C282T, T341C, C481T, G590A, A803G and G857A. Results The wild allele NAT2 *4 was the most prevalent allele (59%) in healthy individuals. The alleles NAT2*6A and NAT2*7B were also frequently observed (21% and 17%, respectively). In contrast to Caucasians, the percentage of slow acetylators was lower (12% in Chinese vs. 58% in Caucasians, P<0.001). No relevant differences were observed for homogenous rapid, heterogeneous rapid/slow and homogeneous slow acetylation genotypes between the healthy subjects and both groups of bladder cancer patients. Conclusion The present work did not support the association of slow acetylating genotypes of NAT2 gene with elevated risk of bladder cancer in Chinese whereas it was documented as an important genetically determined risk factor in Caucasians. Different mechanisms might play a role in individual susceptibility to bladder cancer related with aromatic amine exposure in various races or ethnic groups.

Role of peroxisome proliferator-activated receptors gene polymorphisms in type 2 diabetes and metabolic syndrome

Metabolic syndrome(MetS) and type 2 diabetes mellitus(T2DM) are the serious public health problems worldwide.Moreover,it is estimated that MetS patients have about five-fold greater risk of the T2 DM development compared with people without the syndrome.Peroxisome proliferator-activated receptors are a subgroup of the nuclear hormone receptor superfamily of ligand-activated transcription factors which play an important role in the pathogenesis of MetS and T2 DM.All three members of the peroxisome proliferator-activated receptor(PPAR) nuclear receptor subfamily,PPARα,PPARp/5 and PPARγ are critical in regulating insulin sensitivity,adipogenesis,lipid metabolism,and blood pressure.Recently,more and more studies indicated that the gene polymorphism of PPARs,such as Leu^(162)Val and Val^(227)Ala of PPARα,+294T> C of PPARβ/δ,Pro^(12)Ala and C1431 T of PPARγ,are significantly associated with the onset and progressing of MetS and T2 DM in different population worldwide.Furthermore,a large body of evidence demonstrated that the glucose metabolism and lipid metabolism were influenced by gene-gene interaction among PPARs genes.However,given the complexity pathogenesis of metabolic disease,it is unlikely that genetic variation of a single locus would provide an adequate explanation of inter-individual differences which results in diverse clinical syndromes.Thus,gene-gene interactions and gene-environment interactions associated with T2 DM and MetS need future comprehensive studies.

Identification of a Regulatory Single Nucleotide Polymorphism in the Adiponectin (APM1) Gene Associated with Type 2 Diabetes in Han Nationality

Objective To identify the genetic defects of the the adiponectin （APM1） gene that contribute to the development of type 2 diabetes （T2DM） and determine the functional single nucleotide polymorphisms （SNPs） in the APMI gene associated with T2DM in Han nationality. Methods The APMI gene 5＇-UTR was screened by direct sequencing to identify common polymorphisms. Identified SNPs were genotyped in 585 nondiabetic controls, 278 subjects with impaired glucose intolerance （IGT） and 212 patients with T2DM. The functions of SNPs in the regulatory region were assessed by reporter gene assay. Possible association between SNPs and plasma APMI levels or metabolic parameters was statistically asses,sed. Results Three SNPs were identified in the APMI gene 5＇-UTR. A case-control study revealed that SNP -11377 G/C had significant differences in allele frequencies between T2DM patients and nondiabetic controls （G 0.314/C 0.686 vs. G 0.265/C 0.735, P=0.03）. Haplotype analysis of three SNPs in the APM1 gene showed that no significant association of haplotypes with T2DM. IGT was detected in the present study. Reporter gene assay showed that SNP did not influence the transcription efficiency in the 3T3-LI cell line. Conclusion SNP - 11377 G/C in the proximal promoter region of the APM 1 gene contributes to the development of T2DM in Han nationality but may not be a functional SNP in the APM1 gene.

Association of-238G/A and -857C/T Polymorphisms of Tumor Necrosis Factor-Alpha Gene Promoter Region With Outcomes of Hepatitis B Virus Infection

Objectives To determine whether -238G/A and -857C/T polymorphisms of tumor necrosis factor-alpha （TNF-o0 gene promoter were associated with outcomes of hepatitis B virus infection. Methods A total of 246 HBV self-limited infected subjects and 443 chronic hepatitis B （HB） patients were recruited in this case-control study. TNF-α-238G/A and -857C/T gene promoter polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）. Results The frequency of TNF-α-238 GG （90.7%） in chronic HB group was significantly lower than that （95.1%） in self-limited group （P=0.041）. The frequency of TNF-oc-857 CC （79.7%） in chronic HB patients was significantly higher than that （70.9%） in self-limited infected subjects （P=0.021）. Multiple logistic regression analysis revealed that both TNF-oc-238GA and -857CC were independently associated with chronic HB. Conclusions TNF-α promoter variants are likely to play a substantial role in influencing the outcomes of HBV infection.

TMPRSS2 Polymorphism and Its Correlation with SARS-CoV-2 Susceptibility - A Secondary Publication

Background:Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus affected more people than SARS-CoV-1 and related coronaviruses.Human genetic factors,besides respiratory droplets and direct exposure to the virus,are found highly responsible for transmitting SARS-CoV-2 infection.Aim:The objective of this study was to determine the plasma levels of the TMPRSS2 gene and its role in SARS-CoV-2 susceptibility.Methodology:A total of 100 patients,i.e.50 SARS-CoV-2 positive patients as the case group and 50 SARS-CoV-2 negative samples as the control group,were selected randomly and included in this case-control study to determine the association between TMPRSS2 gene and susceptibility to SARS-CoV-2 infection and severity of coronavirus disease 2019(COVID-19).The TMPRSS2 levels of case and control samples were measured through an enzyme-linked immunosorbent assay(ELISA).Following the genomic DNA extraction,a set of reverse and forward primers of human TMPRSS2 gene primers were used for the amplification of the TMPRSS2 gene.Results:In the control group,the ratio of men to women was more or less the same while in the case group 62%of the population were women.The TMPRSS2 level was found to be 4.70±7.7 ng/ml in case samples while it was 4.73±5.7 ng/ml in control samples.Conclusion:The levels of TMPRSS2 in plasma samples of both controls and cases were found to be the same indicating that the entry of SARS-CoV-2 is not dependent on the plasma levels of this protein.

Clinical significance of NOD2/CARD15 and Toll-like receptor 4 gene single nucleotide polymorphisms in inflammatory bowel disease

AIM： To evaluate the role of genetic factors in the pathogenesis of Crohn＇s disease （CD） and ulcerative colitis （UC）, we investigated the single nucleotide polymorphisms （SNPs） of NOD2/CARD15 （R702W, Gg08R and L1007finsC）, and Toll-like receptor 4 （TLR4） genes （D299G and T399I） in a selected inflammatory bowel disease （IBD） population coming from Southern Italy. METHODS： Allele and genotype frequencies of NOD2/ CARD15 （R702W, Gg08R and L1007finsC） and TLR4 （D299G and T399I） SNPs were examined in 133 CD patients, in 45 UC patients, and in 103 healthy controls. A genotype-phenotype correlation was performed. RESULTS： NOD2/CARD15 R702W mutation was significantly more frequent in CD （9.8%） than in controls （2.4%, P = 0.001） and in UC （2.3%, P = 0.03）. No significant difference was found between UC patients and control group （P 〉 0.05）. In CD and UC patients, no significant association with G908R variant was found. L1007finsC SNP showed an association with CD （9.8%） compared with controls （2.9%, P = 0.002） and UC patients （2.3%, P = 0.01）. Moreover, in CD patients, G908R and L1007finsC mutations were significantly associated with different phenotypes compared to CD wild-type patients. No association of IBD with the TLR4 SNPs was found in either cohort （allele frequencies： D299G-controls 3.9%, CD 3.7%, UC 3.4%, P 〉 0.05; T399I-controls 2.9%, CD 3.0%, UC 3.4%, P 〉 0.05）. CONCLUSION： These findings confirm that, in our IBD patients selected from Southern Italy, the NOD2/ CARD15, but not TLR4 SNPs, are associated with increased risk of CD.

WJD 5^(th) Anniversary Special Issues(2): Type 2 diabetes Genetic polymorphisms of cytokine genes in type 2 diabetes mellitus

Diabetes mellitus is a combined metabolic disorder which includes hyperglycemia,dyslipidemia,stroke and several other complications.Various groups all over the world are relentlessly working out the possible role of a vast number of genes associated with type 2 diabetes(T2DM).Inflammation is an important outcome of any kind of imbalance in the body and is therefore an indicator of several diseases,including T2DM.Various ethnic populations around the world show different levels of variations in single nucleotide polymorphisms(SNPs).The present review was undertaken to explore the association of cytokine gene polymorphisms with T2DM in populations of different ethnicities.This will lead to the understanding of the role of cytokine genes in T2DM risk and development.Association studies of genotypes of SNPs present in cytokine genes will help to identify risk haplotype(s)for disease susceptibility by developing prognostic markers and alter treatment strategies for T2DM and related complications.This will enable individuals at risk to take prior precautionary measures and avoid or delay the onset of the disease.Future challenges will be to understand the genotypic interactions between SNPs in one cytokine gene or several genes at different loci and study their association with T2DM.