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.

Population-based carrier screening and prenatal diagnosis of fragile X syndrome in East Asian populations

Identification of carriers of fragile X syndrome(FXS) with the subsequent prenatal diagnosis and knowledge of FXS-associated genetic profiles are essential for intervention in specific populations. We report the results of carrier screening of 39,458 East Asian adult women and prenatal diagnosis from 87 FXS carriers.The prevalence of FXS carriers and full mutation fetuses was estimated to be 1/581 and 1/3124 in East Asian populations, respectively. We confirmed the validity of the current threshold of CGG trinucleotide repeats for FMR1 categorization;the integral risks of full mutation expansion were approximately 6.0%,43.8%, and 100% for premutation alleles with 55—74, 75—89, and ≥ 90 CGG repeats, respectively. The protective effect of AGG(adenine-guanine-guanine nucleotides) interruption in East Asian populations was validated, which is important in protecting premutation alleles with 75—89 CGG repeats from full mutation expansion. Finally, family history was shown not an effective indicator for FXS carrier screening in East Asian populations, and population-based screening was more cost-effective. This study provides an insight into the largest carrier screening and prenatal diagnosis for FXS in East Asian populations to date. The FXSassociated genetic profiles of East Asian populations are delineated, and population-based carrier screening is shown to be promising for FXS intervention.

Identification of novel loci influencing refractive error in East Asian populations using an extreme phenotype design

The global "myopia boom" has raised significant international concerns. Despite a higher myopia prevalence in Asia, previous large-scale genome-wide association studies(GWASs) were mostly based on European descendants. Here, we report a GWAS of spherical equivalent(SE) in 1852 Chinese Han individuals with extreme SE from Guangzhou(631 <-6.00 D and 574 > 0.00 D) and Wenzhou(593 <-6.00 D and54 >-1.75 D), followed by a replication study in two independent cohorts with totaling 3538 East Asian individuals. The discovery GWAS and meta-analysis identify three novel loci, which show genome-wide significant associations with SE, including 1 q25.2 FAM163 A, 10 p11.22 NRP1/PRAD3, and 10 p11.21 ANKRD30 A/MTRNR2 L7, together explaining 3.34% of SE variance. 10 p11.21 is successfully replicated.The allele frequencies of all three loci show significant differences between major continental groups(P < 0.001). The SE reducing(more myopic) allele of rs10913877(1 q25.2 FAM163 A) demonstrates the highest frequency in East Asians and much lower frequencies in Europeans and Africans(EAS = 0.60,EUR = 0.20, and AFR = 0.18). The gene-based analysis additionally identifies three novel genes associated with SE, including EI24, LHX5, and ARPP19. These results provide new insights into myopia pathogenesis and indicate the role of genetic heterogeneity in myopia epidemiology among different ethnicities.

Population and Food in Asian Developing Countries

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Dabigatran,rivaroxaban,and apixaban are superior to warfarin in Asian patients with non-valvular atrial fibrillation:An updated metaanalysis

BACKGROUND Most of the randomized clinical trials that led to the wide use of non-vitamin K antagonist oral anticoagulants for stroke prevention in patients with atrial fibrillation(AF)originated from western countries.AIM To systematically review and quantitatively synthesize the real-world data regarding the efficacy and safety of dabigatran,rivaroxaban,and apixaban compared to warfarin for stroke prevention in Asian patients with non-valvular AF.METHODS Medline,Cochrane,and ClinicalTrial.gov databases were reviewed.A randomeffect model meta-analysis was used and I-square was utilized to assess the heterogeneity.The primary outcome was ischemic stroke.The secondary outcomes were all-cause mortality,major bleeding,intracranial hemorrhage,and gastrointestinal bleeding.RESULTS Twelve studies from East Asia or Southeast Asia and 441450 patients were included.Dabigatran,rivaroxaban,and apixaban were associated with a significant reduction in the incidence of ischemic stroke[hazard ratio(HR)=0.78,95%confidence interval(CI):0.65-0.94;HR=0.79,95%CI:0.74-0.85,HR=0.70,95%CI:0.62-0.78;respectively],all-cause mortality(HR=0.68,95%CI:0.56-0.83;HR=0.66,95%CI:0.52-0.84;HR=0.66,95%CI:0.49-0.90;respectively),and major bleeding(HR=0.61,95%CI:0.54-0.69;HR=0.70,95%CI:0.54-0.90;HR=0.58,95%CI:0.43-0.78;respectively)compared to warfarin.CONCLUSION Dabigatran,rivaroxaban,and apixaban appear to be superior to warfarin in both efficacy and safety in Asians with non-valvular AF.

Association of MBOAT7 rs641738 polymorphism with hepatocellular carcinoma susceptibility:A systematic review and meta-analysis

BACKGROUND The MBOAT7 rs641738 single-nucleotide polymorphism(SNP)has been proven to influence various liver diseases,but its association with hepatocellular carcinoma(HCC)susceptibility has been debated.To address this discrepancy,we conducted the current systematic review and meta-analysis.AIM To perform a systematic review and meta-analysis on association of MBOAT7 SNP and HCC susceptibility.METHODS We performed a systematic review in PubMed,Web of Science,Scopus,and EMBASE;applied specific inclusion and exclusion criteria;and extracted the data.Meta-analysis was conducted with the meta package in R.Sensitivity and subgroup analyses were also performed.This meta-analysis was registered in PROSPERO(CRD42023458046).RESULTS Eight studies were included in the systematic review,and 12 cohorts from 6 studies were included in the meta-analysis.Our meta-analysis revealed an association between the MBOAT7 SNP and HCC susceptibility in both the dominant[odds ratio(OR):1.14,95%confidence interval(95%CI):1.02-1.26,P=0.020]and recessive(OR:1.21,95%CI:1.05-1.39,P=0.008)models.Subgroup analysis revealed that stratification of the included patients by geographical origin showed a significant association in Asia(OR:1.20,95%CI:1.03-1.39).CONCLUSION This meta-analysis underscores the contribution of the MBOAT7 rs641738 SNP to hepatocarcinogenesis,especially in Asian populations,which warrants further investigation.

Prostate cancer in Asia:A collaborative report

The incidence of prostate cancer(PCa)within Asian population used to be much lower than in the Western population;however,in recent years the incidence and mortality rate of PCa in some Asian countries have grown rapidly.This collaborative report summarized the latest epidemiology information,risk factors,and racial differences in PCa diagnosis,current status and new trends in surgery management and novel agents for castration-resistant prostate cancer.We believe such information would be helpful in clinical decision making for urologists and oncologists,health-care ministries and medical researchers.

Gender differences in clinical outcomes of acute myocardial infarction undergoing percutaneous coronary intervention: insights from the KAMIR-NIH Registry

Background There are numerous but conflicting data regarding gender differences in outcomes following percutaneous coronary intervention(PCI). Furthermore, gender differences in clinical outcomes with acute myocardial infarction(AMI) following PCI in Asian population remain uncertain because of the under-representation of Asian in previous trials. Methods A total of 13,104 AMI patients from Korea Acute Myocardial Infarction Registry-National Institute of Health(KAMIR-NIH) between November 2011 and December 2015 were classified into male(n = 8021, 75.9%) and female(n = 2547, 24.1%). We compared the demographic, clinical and angiographic characteristics, 30-days and 1-year major adverse cardiac and cerebrovascular events(MACCE) in women with those in men after AMI by using propensity score(PS) matching. Results Compared with men, women were older, had more comorbidities and more often presented with non-ST segment elevation myocardial infarction(NSTEMI) and reduced left ventricular systolic function. Over the median follow-up of 363 days, gender differences in both 30-days and 1-year MACCE as well as thrombolysis in myocardial infarction minor bleeding risk were not observed in the PS matched population(30-days MACCE: 5.3% vs. 4.7%, log-rank P = 0.494, HR = 1.126, 95% CI: 0.800-1.585;1-year MACCE: 9.3% vs. 9.0%, log-rank P = 0.803, HR = 1.032, 95% CI: 0.802-1.328;TIMI minor bleeding: 4.9% vs. 3.9%, log-rank P = 0.215, HR = 1.255, 95% CI: 0.869-1.814). Conclusions Among Korean AMI population undergoing contemporary PCI, women, as compared with men, had different clinical and angiographic characteristics but showed similar 30-days and 1-year clinical outcomes. The risk of bleeding after PCI was comparable between men and women during one-year follow up.

Cytogenetic Profile in 7209 Indian Patients with de novo Acute Leukemia: A Single Centre Study from India

Background: Cytogenetics is one of the most important diagnostic parameters in the classification of acute leukemia. Recurrent chromosomal aberrations in acute leukemia have provided insights into the molecular mechanism of leukemogenesis. The variable frequencies of recurrent cytogenetic markers due to ethical/racial differences have been reported from Western and some Asian countries. Objective: We report cytogenetic data of largest cohort of 7209 adult and pediatric patients with de novo acute leukemia (AL) to determine the prevalence of various cytogenetic sub groups and compare with the Western and Asian population. Material & Methods: The AL patients included 2609 AML (adult: 2042, pediatric: 567), 3708 B-cell-precursor (BCP)-ALL (adult: 1300, pediatric: 2408) and 892 cases of T-ALL (adult: 480, pediatric: 412). Cytogenetic studies included conventional karyotyping and FISH using panel of probes. Results: The incidence of t(8;21) was high, comparable to other Asian countries. In comparison to our series and Western population, t(15;17) was more prevalent in Chinese population. Cytogenetic profiling of BCP-ALL revealed low prevalence of ETV6/RUNX1 in ours as well as other Asian population. The MLL aberrations in BCP-ALL and TLX1 & TLX3 aberrations in T-ALL occurred less frequently in our series as compared with Western population. Conclusion: The present study with a large cohort showed the heterogeneity of AL that involved various factors, such as age, gender and prevalence of distinct cytogenetic subgroups. Our data in comparison with other population based studies revealed differential distribution of some cytogenetic sub-groups indicating geographic heterogeneity due to differential environmental exposure which probably influenced underlying genetic susceptibility.

Multi-link Vision and MiniVision stent registry in Asian patients with coronary artery disease:a prospective,multi-center study

Background Recent studies have showed that the fine mesh stents are associated with a significant reduction in both clinical and angiographic re-stenosis of the coronary arteries. To maintain a very satisfactory radio-opacity using the stents, Guidant of the USA has designed a new type of bare metal stents （BMS）-Multi-link （ML） Vision / ML MiniVision stents. The clinical outcomes of Asian patients with coronary artery disease （CAD） after implanting the Multi-link Vision or MiniVision stent were investigated in this study. Methods An observational, prospective, multi-center, non-randomized post marketing registry was conducted to demonstrate the efficacy of the BMS- ML Vision / ML MiniVision stents. The primary end point of the registry was clinical target lesion revascularization （TLR） at a 6-month follow-up. The major secondary end points included the rate of major adverse cardiac events （MACE） and serious adverse events （SAE） in hospital and at 6 months; and the rate of clinical TLR as a function of the type of angina. A total of 429 Asian people with 449 lesions from 14 centers were selected for this study, The average reference diameter of the lesions was （3.0±0.5） mm, and the mean length was （15.7±5.0） mm. Results The successful rate of the procedure was 99.3%. Twenty-five percent of the lesions were treated by direct stenting without pre-dilation. Eighty-six percent of the lesions were implanted with ML Vision stent. After the 6-month follow-up, the rate of clinical TLR was 1.4%. The MACE, SAE and target vessel revascularization （TVR） were 6.8%, 3.5% and 1.4% respectively. Conclusion The current registry showed the excellent 6-month clinical outcomes of ML Vision/ML MiniVision stents in Asian patients with CAD.

First Trimester Screening for Preeclampsia:An Asian Perspective

Preeclampsia(PE)is one of the leading causes of maternal and perinatal morbidity and mortality worldwide.This disorder has profound short-term and long-term impacts on both the affected woman’s and her child’s health.Early-onset PE requiring preterm delivery(preterm PE)is of particular importance because it is associated with a higher risk of adverse pregnancy outcomes than term PE.First trimester screening model developed by the Fetal Medicine Foundation(FMF),which uses Bayes-theorem to combine maternal characteristics and medical history together with measurements of mean arterial pressure,uterine artery pulsatility index,and serum placental growth factor,has been proven to be effective and have superior screening performance to that of traditional risk factor-based approach for the prediction of PE.Identification of high risk pregnant women for preterm PE and giving aspirin prophylaxis before 16^(th)week of gestation would reduce the incidence of preterm PE.In Asia,although the prevalence of PE is slightly lower than the global estimation,early screening and prevention of this life-threatening condition is still crucial.The FMF Bayestheorem based screening method has been validated in a large-scale prospective Asia-wide study and revealed that the first trimester triple test achieves the highest detection rate,compared with the traditional risk factor-based approaches,and that the screening performance is comparable to the published data from the FMF in East Asian women.However,in order to achieve optimal screening performance,the key is to establish standardized methods for biomarker measurements and regular biomarker quality assessment,as each biomarker is susceptible to inaccurate measurement,thus affecting performance of screening.Furthermore,it is of great importance to emphasize that the optimal preventive effect of aspirin on preterm PE is clearly associated with good compliance to treatment.In conclusion,global implementation of an effective first trimester“screen and prevent”program for preterm PE would provide the opportunity to reduce the risk of both short-term maternal and perinatal morbidity and mortality,with the possibility of intergenerational prevention of future chronic diseases for both the mother and her offspring.

Plasma Lipidomic Subclasses and Risk of Hypertension in Middle-Aged and Elderly Chinese

While disrupted lipid metabolism is a well-established risk factor for hypertension in animal models,the links between various lipidomic signatures and hypertension in human studies remain unclear.We aimed to examine associations between plasma lipidomic profiles and prevalence of hypertension among 2248 community-living Chinese aged 50-70 years.Hypertension was defined according to 2020 International Society of Hypertension global hypertension practice guidelines and 2018 Chinese guidelines.In total,728 plasma lipidomic species were profiled using high-coverage targeted lipidomics.After multivariate adjustment,including lifestyle,body mass index,blood lipids,and sodium intake,110 metabolites from nine lipidomic subclasses showed significant associations with hypertension,among which phosphatidylethanolamines(PEs)had the strongest association.Eleven lipidomic signals for hypertension risk were further identified from the nine subclasses,including PE(18:0/18:2)(OR per SD,1.49;95%confidence intervals,1.30-1.69),phosphatidylcholine(PC)(18:0/18:2)(1.27;1.13-1.43),phosphatidylserine(18:0/18:0)(1.24;1.09-1.41),lysophosphatidylinositol(18:1)(1.17;1.06-1.29),triacylglycerol(52:5)(1.38;1.18-1.61),diacylglycerol(16:0/18:2)(1.42;1.19-1.69),dihydroceramide(24:0)(1.25;1.09-1.43),hydroxyl-sphingomyelins(SM[2OH])C34:1(1.19;1.07-1.33),lysophosphatidylcholine(20:1)(0.86;0.78-0.95),SM(OH)C38:1(0.87;0.79-0.96),and PC(18:2/20:1)(0.84;0.75-0.94).Principal component analysis also showed that a factor mainly containing specific PEs was positively associated with hypertension(1.20;1.09-1.33).Collectively,our study revealed that disturbances in multiple circulating lipidomic subclasses and signatures,especially PEs,were significantly associated with the prevalence of hypertension in middle-aged and elderly Chinese.Future studies are warranted to confirm our findings and determine the mechanisms underlying these associations.