Association between Diabetes and Risk of Aortic Dissection: A Case-Control Study in a Chinese Population

Background

It is well-recognized that diabetes represents a powerful independent risk factor for cardiovascular diseases. However, very few studies have investigated the relationship between diabetes and risk of aortic dissection (AD).

Aim

The aim of this case-control study was to evaluate the association between diabetes and risk of AD in Chinese population.

Methods

A hospital-based case-control study, consisting of 2160 AD patients and 4320 controls, was conducted in a Chinese population. Demographic, clinical characteristics and risk factors were collected. Diabetes rate of patients with overall AD, Stanford type A AD and type B AD group was compared with that of corresponding matched control groups. Logistic regression analysis was used to estimate the odds ratios (OR) and 95% confidence intervals (95% CI) for relationship between diabetes and AD risk.

Results

The prevalence of diabetes was lower in AD cases than that of control subjects, whether it is the overall AD, type A AD or type B AD group (4.7% vs. 10.0%, 2.9% vs. 8.8%, 5.9% vs. 10.9%, all P<0.001). Furthermore, in multivariate model, diabetes was found to be associated with lower AD risk, which not only applies to the overall AD (OR = 0.2, 95%CI: 0.15–0.26), but also type A AD (OR = 0.12, 95% CI: 0.07–0.20) and type B AD (OR = 0.25, 95%CI: 0.18–0.33).

Conclusions

We observed the paradoxical inverse relationship between DM and risk of AD in the Chinese population. These results suggest diabetes may play a protective role in the development of AD. However, further studies are needed to enrich related evidence, especially with regard to underlying mechanisms for these trends.     

The Association Between First-Degree Family History of Diabetes and Metabolic Syndrome

Objective: Because they share genetic and environmental factors with patients with diabetes, the first-degree relatives (FDRs) of patients with diabetes exhibit early signs of metabolic abnormalities. The present study aimed to investigate the correlation between family history of diabetes in FDRs and metabolic syndrome (MS), as well as changes in related risk factors.Methods: The present study population was a part of the baseline survey from the REACTION study. FDRs were defined as individuals having one or more FDRs with diabetes. MS and its components were defined according to the 2007 Joint Committee for Developing Chinese Guidelines.Results: A total of 2,692 individuals with an average age of 57.24 ± 8.35 years were enrolled in the present study. The prevalence of MS in FDRs (36.44%) was significantly higher than that in non-FDRs (25.28%; P<.001). FDRs accounted for 13.37%, 14.32%, 16.67%, 22.47%, 23.53%, and 25.58% of subjects with 0 to 5 MS components, showing an increasing trend (P for trend <.001). After adjusting for gender and age, partial correlation analyses showed significant associations of first-degree family history of diabetes with MS-related indexes (all P<.05). After adjusting for gender, age, lifestyle habits, and total metabolic traits, the first-degree family history of diabetes remained an independent factor that was positively associated with MS (odds ratio, 1.765; P<.001).Conclusion: A first-degree family history of diabetes predisposes individuals to developing MS and stands out as an independent risk factor for MS even without considering the subsequent effects of hyperglycemia.Abbreviations: BMI = body mass index; DBP = diastolic blood pressure; FDR = first-degree relative; FPG = fasting plasma glucose; HbA1c = glycated hemoglobin A1c; HDL-c = high-density-lipoprotein cholesterol; LDL-c = low-density-lipoprotein cholesterol; MAP = mean arterial pressure; MS = metabolic syndrome; OR = odds ratio; SBP = systolic blood pressure; TC = total cholesterol; TG = triglyceride; WC = waist circumference; WHR = waist-to-hip ratio; 2hPG = 2-hour plasma glucose     

Prevalence,Awareness, Treatment and Control of Diabetes Mellitus in a Chinese Population

ObjectiveThe purpose of this study is to evaluate the prevalence, awareness, treatment and glycemic control of diabetes mellitus (DM) in a Chinese population. The findings from this study are expected to offer scientific evidence to better prevent and control the growing number of reported and untreated cases.MethodsA cross-sectional survey was conducted in Jiangsu, China. We recruited permanent residents over 18 years of age from eight towns in Jintan (JT) and six towns in Yangzhong (YZ) using a three-stage stratified cluster sampling method. The rates of DM prevalence, awareness, treatment and control as well as their related factors were analyzed.ResultsA total number of 15404 people were entered into the analysis. The DM prevalence, awareness, treatment and control rates were 7.31%, 58.35%, 51.87% and 14.12%, respectively. Multivariable logistic regression analysis showed that being female was positively related to prevalence (OR = 1.21, 95% CI: 1.07–1.37), awareness (OR = 1.52, 95% CI: 1.19–1.93), treatment (OR = 1.48, 95% CI: 1.17–1.88) and control (OR = 1.87, 95% CI: 1.30–2.67) of DM. Having a family history of diabetes was significantly correlated with DM risk (OR = 1.86, 95% CI: 1.37–2.54) and increased awareness (OR = 3.12, 95% CI: 2.19–4.47), treatment (OR = 3.47, 95% CI: 2.45–4.90) and control (OR = 1.81, 95% CI: 1.22–2.68) of DM. Former smoking status (OR = 1.82, 95% CI: 1.23–2.71), overweight (OR = 2.11, 95% CI: 1.72–2.60) and obesity (OR = 3.46, 95% CI: 2.67–4.50) were related to the risk of DM. Additionally, we found current drinking status to be positively correlated with DM risk (OR = 1.30, 95% CI: 1.01–1.66) and negatively correlated with DM awareness (OR = 0.41, 95% CI: 0.29–0.59) and treatment (OR = 0.41, 95% CI: 0.29–0.59). Our study highlights the high prevalence and inadequate awareness, treatment and control of DM in the Chinese population.ConclusionsManagement and prevention of DM-related complications should be considered an essential strategy by governments and society. This study assessed the reasons why DM has been increasing and established the first step in determining where to start regarding preventative methods.     

Impact of Family History of Diabetes on Diabetes Control and Complications

Objective: Our aim was to assess the impact of parental and sibling history of type 2 diabetes (T2D) on patient characteristics, glycemic control, and T2D complications.Methods: This cross-sectional study included adults with T2D. Type 1 diabetes and gestational diabetes patients were excluded. The laboratory data were retrieved from the patients' electronic files, and baseline measurements were obtained by the researchers.Results: The study included a total of 511 T2D patients, with a mean age of 60.1 ± 10.9 years and mean hemoglobin A1c of 8.94 ± 2.1% (74.2 ± 22.9 mmol/mol). Of these patients, 54% were male and 49.7% had a parental history of T2D. The patients with parental history of T2D were diagnosed at a younger age and had a higher body mass index (BMI) (P =.035) and higher waist circumference (WC) (P =.013) than those T2D patients with no parental history. Approximately 60% of the participants had siblings with a history of T2D, and in comparison with those with no sibling history, they had higher prevalence of cerebrovascular accidents (P =.02).Conclusion: Having a parental history of T2D is significantly associated with diagnosis at a younger age and a higher BMI and WC. Having a sibling history of T2D is significantly associated with worse cerebrovascular outcome.Abbreviations: ACR = albumin to creatinine ratio; BMI = body mass index; DBP = diastolic blood pressure; DM = diabetes mellitus; FBG = fasting blood glucose; GFR = glomerular filtration rate; HbA1c = hemoglobin A1c; LDL = low-density lipoprotein; SBP = systolic blood pressure; T2D = type 2 diabetes; TG = triglyceride; WC = waist circumference     

Association of Genetic Markers in the BCL-2 Family of Apoptosis-Related Genes with Endometrial Cancer Risk in a Chinese Population

BackgroundIn vitro studies have demonstrated the role of the BCL-2 family of genes in endometrial carcinogenesis. The role of genetic variants in BCL-2 genes and their interactions with non-genetic factors in the development of endometrial cancer has not been investigated in epidemiological studies.ResultsSignificant associations with endometrial cancer risk were found for 9 SNPs in the BCL2 gene (P trend<0.05 for all). For SNPs rs17759659 and rs7243091 (minor allele for both: G), the associations were independent. The odds ratio was 1.27 (95% CI: 1.04–1.53) for women with AG genotype for the SNP rs17759659 and 1.82 (95% CI: 1.21–2.73) for women with the GG genotype for the SNP rs7243091. No interaction between these two SNPs and established non-genetic risk factors of endometrial cancer was noticed.ConclusionGenetic polymorphisms in the BCL2 gene may be associated with the risk of endometrial cancer in Chinese women.     

Validation of Type 2 Diabetes Risk Variants Identified by Genome-Wide Association Studies in Han Chinese Population: A Replication Study and Meta-Analysis

Background

Several genome-wide association studies (GWAS) involving European populations have successfully identified risk genetic variants associated with type 2 diabetes mellitus (T2DM). However, the effects conferred by these variants in Han Chinese population have not yet been fully elucidated.

Methods

We analyzed the effects of 24 risk genetic variants with reported associations from European GWAS in 3,040 Han Chinese subjects in Taiwan (including 1,520 T2DM cases and 1,520 controls). The discriminative power of the prediction models with and without genotype scores was compared. We further meta-analyzed the association of these variants with T2DM by pooling all candidate-gene association studies conducted in Han Chinese.

Results

Five risk variants in IGF2BP2 (rs4402960, rs1470579), CDKAL1 (rs10946398), SLC30A8 (rs13266634), and HHEX (rs1111875) genes were nominally associated with T2DM in our samples. The odds ratio was 2.22 (95% confidence interval, 1.81-2.73, P<0.0001) for subjects with the highest genetic score quartile (score>34) as compared with subjects with the lowest quartile (score<29). The incoporation of genotype score into the predictive model increased the C-statistics from 0.627 to 0.657 (P<0.0001). These estimates are very close to those observed in European populations. Gene-environment interaction analysis showed a significant interaction between rs13266634 in SLC30A8 gene and age on T2DM risk (P<0.0001). Further meta-analysis pooling 20 studies in Han Chinese confirmed the association of 10 genetic variants in IGF2BP2, CDKAL1, JAZF1, SCL30A8, HHEX, TCF7L2, EXT2, and FTO genes with T2DM. The effect sizes conferred by these risk variants in Han Chinese were similar to those observed in Europeans but the allele frequencies differ substantially between two populations.

Conclusion

We confirmed the association of 10 variants identified by European GWAS with T2DM in Han Chinese population. The incorporation of genotype scores into the prediction model led to a small but significant improvement in T2DM prediction.     

Prevalence of Metabolic Syndrome: Association with Risk Factors and Cardiovascular Complications in an Urban Population

Introduction

Metabolic syndrome (MS) is a set of cardiovascular risk factors and type 2 diabetes, responsible for a 2.5-fold increased cardiovascular mortality and a 5-fold higher risk of developing diabetes.

Objectives

1-to evaluate the prevalence of MS in individuals over 18 years associated with age, gender, socioeconomic status, educational levels, body mass index (BMI), HOMA index and physical activity; moreover, to compare it to other studies; 2-to compare the prevalence of elevated blood pressure (BP), high triglycerides and plasma glucose levels, low HDL cholesterol and high waist circumference among individuals with MS also according to gender; 3-to determine the number of risk factors in subjects with MS and prevalence of complications in individuals with and without MS aged over 40 years.

Methods

A cross-sectional study of 1369 Individuals, 667 males (48.7%) and 702 females (51.3%) was considered to evaluate the prevalence of MS and associated factors in the population.

Results

The study showed that 22.7% (95% CI: 19.4% to 26.0%) of the population has MS, which increases with age, higher BMI and sedentary lifestyle. There was no significant difference between genders until age ≥70 years and social classes. Higher prevalence of MS was observed in lower educational levels and higher prevalence of HOMA positive among individuals with MS. The most prevalent risk factors were elevated blood pressure (85%), low HDL cholesterol (83.1%) and increased waist circumference (82.5%). The prevalence of elevated BP, low HDL cholesterol and plasma glucose levels did not show significant difference between genders. Individuals with MS had higher risk of cardiovascular complications over 40 years.

Conclusion

The prevalence of MS found is similar to that in developed countries, being influenced by age, body mass index, educational levels, physical activity, and leading to a higher prevalence of cardiovascular complications after the 4th decade of life.     

Family History of Diabetes is Associated with Increased Risk of Recurrent Diabetic Ketoacidosis in Pediatric Patients

Objective: To determine the relationship between family history of diabetes mellitus (DM) and diabetic ketoacidosis (DKA) recurrence in youth with established type 1 diabetes mellitus (T1DM).Methods: We performed a retrospective chart review of patients with DKA admitted to a pediatric hospital between January, 2009, and December, 2014. We compared patients with recurrent (≥2 admissions) and nonrecurrent DKA (1 admission) and investigated patient level factors, including family history, that may be associated with DKA recurrence in pediatric patients with established T1DM.Results: Of the 131 subjects in the study, 51 (39%) subjects were in the recurrence group. Age ≥15 years old, public health insurance, and family history of T1DM or type 2 diabetes mellitus were associated with recurrent DKA admissions in both univariable and multivariable analyses. Family history was associated with DKA recurrence, with an incidence rate ratio of 1.5 (95% confidence interval = 1.0 to 2.3; P = .03). The association was not explained by type of familial diabetes, first degree relative status, or whether the family member lived in the household.Conclusion: Recognition that a positive family history of DM may be associated with a higher risk for DKA recurrence in patients with established T1DM may allow for targeted education and focus on a previously unidentified population at increased risk for DKA. Understanding the mechanism underlying the effect of family history of diabetes on the rates of DKA in patients with established T1DM may allow for improved identification and education of patients who may be at risk for DKA recurrence.Abbreviations: CI = confidence interval; DKA = diabetic ketoacidosis; EHR = electronic health record; IBD = inflammatory bowel disease; IRR = incidence rate ratio; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus     

Association between Lipid Ratios and Insulin Resistance in a Chinese Population

Aim

To explore the association of lipid ratios and triglyceride (TG) with insulin resistance (IR) in a Chinese population. We also provide the clinical utility of lipid ratios to identify men and women with IR.

Methods

This cross-sectional study included 614 men and 1055 women without diabetes. Insulin resistance was defined by homeostatic model assessment of IR > 2.69. Lipid ratios included the TG/ high density lipoprotein cholesterol (HDL-C), the total cholesterol (TC)/HDL-C and the low density lipoprotein cholesterol (LDL-C)/HDL –C. Logistic regression models and accurate estimates of the area under the receiver operating characteristic (AUROC) curves were obtained.

Results

In normal-weight men, none of lipid ratios nor TG was associated with IR. In overweight/obese men, normal-weight women and overweight/obese women, the TG/HDL-C, the TC/HDL-C and TG were significantly associated with IR, and the associations were independent of waist circumference. All of the AUROCs for the TG/HDL-C and TG were > 0.7. The AUROCs for TC/HDL-C ratio were 0.69–0.77. The optimal cut-offs for TG/HDL-C were 1.51 in men and 0.84 in women. The optimal cut-offs for TG were 1.78 mmol/L in men and 1.49 mmol/L in women, respectively. In men, the optimal cut-off for LDL-C/HDL-C is 3.80. In women, the optimal cut-off for LDL-C/HDL-C is 3.82.

Conclusion

The TG/HDL-C, the TC/HDL-C and TG are associated with IR in overweight/obese men, normal-weight and overweight/obese women. The LDL-C/HDL-C is only associated with IR in normal-weight women. The TG/HDL-C and TG might be used as surrogate markers for assessing IR.     

There Is No Association between MicroRNA Gene Polymorphisms and Risk of Triple Negative Breast Cancer in a Chinese Han Population

Triple-negative breast cancer (TNBC) is defined by the lack of the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). It is characterized by aggressive behavior, poor prognosis and lack of targeted therapies. MicroRNA (miRNA) as a novel modulator of gene expression has played an important regulatory role in the malignancy. Dysregulation and/or mutation of the miRNAs may also contribute to the TNBC susceptibility since it is associated with the expression of ER, PR and HER2. Single nucleotide polymorphisms (SNPs) in miRNAs may be extremely relevant for TNBC. We tried to validate the hypothesis that genetic variations in miRNA are associated with TNBC development, and identify candidate biomarkers for TNBC susceptibility and clinical treatment. We screened the genetic variants in all miRNA genes listed in the public database miRBase and NCBI. A total of 23 common SNPs in 22 miRNAs, which tagged the known common variants in the Chinese Han people with a minor allele frequency greater than 0.05, were genotyped. This case-control study involved 191 patients with TNBC and 192 healthy female controls. Frequencies of SNPs were compared between cases and controls to identify the SNPs associated with TNBC susceptibility. No significant association was found between TNBC risk and the SNPs in the miRNA genes in the Chinese Han people (P>0.05), but this warrants further studies.     

Genetic Variants of TPCN2 Associated with Type 2 Diabetes Risk in the Chinese Population

Objective

The aim of this study was to determine whether TPCN2 genetic variants are associated with type 2 diabetes and to elucidate which variants in TPCN2 confer diabetes susceptibility in the Chinese population.

Research Design and Methods

The sample population included 384 patients with type 2 diabetes and 1468 controls. Anthropometric parameters, glycemic and lipid profiles and insulin resistance were measured. We selected 6 TPCN2 tag single nucleotide polymorphisms (rs35264875, rs267603153, rs267603154, rs3829241, rs1551305, and rs3750965). Genotypes were determined using a Sequenom MassARRAY SNP genotyping system.

Results

Ultimately, we genotyped 3 single nucleotide polymorphisms (rs3750965, rs3829241, and rs1551305) in all individuals. There was a 5.1% higher prevalence of the rs1551305 variant allele in type 2 diabetes individuals (A) compared with wild-type homozygous individuals (G). The AA genotype of rs1551305 was associated with a higher diabetes risk (p<0.05). The distributions of rs3829241 and rs3750965 polymorphisms were not significantly different between the two groups. HOMA-%B of subjects harboring the AA genotype of rs1551305 decreased by 14.87% relative to the GG genotype.

Conclusions

TPCN2 plays a role in metabolic regulation, and the rs1551305 single nucleotide polymorphism is associated with type 2 diabetes risk. Future work will begin to unravel the underlying mechanisms.     

Association between the Polymorphism rs3217927 of CCND2 and the Risk of Childhood Acute Lymphoblastic Leukemia in a Chinese Population

CyclinD proteins, the ultimate recipients of mitogenic and oncogenic signals, play a crucial role in cell-cycle regulation. CyclinD2, one of the cyclinD family, is overexpressed in T-acute lymphoblastic leukemia (ALL) and B-cell chronic lymphocytic leukemia and involved in the pathogenesis of leukemias. Recent reports indicated that CCND2 polymorphisms are associated with human cancer risk, thusly we hypothesized that CCND2 gene polymorphisms may contribute to childhood ALL susceptibility. We selected the polymorphism rs3217927 located in the 3′UTR region of CCND2 to assess its associations with childhood ALL risk in a case-control study. A significant difference was found in the genotype distributions of rs3217927 polymorphism between cases and controls (P = 0.019) and homozygous GG genotype may be an increased risk factor for childhood ALL (adjusted OR  =  1.84, 95% CI  =  1.14 —2.99). Furthermore, this increased risk was more pronounced with GG genotype among high-risk ALL (adjusted OR  = 1.95, 95% CI  =  1.04–3.67), low-risk ALL (adjusted OR  =  2.09, 95% CI  =  1.13–3.87), B-phenotype ALL patients (adjusted OR  =  1.78, 95% CI  =  1.08–2.95) and T-phenotype ALL patients (adjusted OR  =  2.87, 95% CI  =  1.16–7.13). Our results provide evidence that CCND2 polymorphism rs3217927 may be involved in the etiology of childhood ALL, and the GG genotype of rs3217927 may modulate the genetic susceptibility to childhood ALL in the Chinese population. Further functional studies and investigations in larger populations should be conducted to validate our findings.     

An Exploratory Study of the Association between KCNB1 rs1051295 and Type 2 Diabetes and Its Related Traits in Chinese Han Population

Since the KCNB1 encoding Kv2.1 channel accounts for the majority of Kv currents modulating insulin secretion by pancreatic islet beta-cells, we postulated that KCNB1 is a plausible candidate gene for genetic variation contributing to the variable compensatory secretory function of beta-cells in type-2 diabetes (T2D). We conducted two studies, a case-control study and a cross-section study, to investigate the association of common single-nucleotide polymorphisms (SNPs) in KCNB1 with T2D and its linking traits. In the case-control study, we first examined the association of 20 tag SNPs of KCNB1 with T2D in a population with 226 T2D patients and non-diabetic subjects (screening study). We then identified the association in an enlarged population of 412 T2D patients and non-diabetic subjects (replication study). In the cross-sectional study, we investigated the linkage between the candidate SNP rs1051295 and T2D by comparing beta-cell function and insulin sensitivity among rs1051295 genotypes in a general population of 1051 subjects at fasting and after glucose loading (oral glucose tolerance tests, OGTT) in 84 fasting glucose impaired subjects, and several T2D-related traits. We found that among the 19 available tag SNPs, only the KCNB1 rs1051295 was associated with T2D (P = 0.027), with the rs1051295 TT genotype associated with an increased risk of T2D compared with genotypes CC (P = 0.009). At fasting, rs1051295 genotype TT was associated with a 9.8% reduction in insulin sensitivity compared to CC (P = 0.008); along with increased plasma triglycerides (TG) levels (TT/CC: P = 0.046) and increased waist/hip (W/H) ratio (TT/CC: P = 0.013; TT/TC: P = 0.002). OGTT confirmed that genotype TT exhibited reduced insulin sensitivity by 16.3% (P = 0.030) compared with genotype TC+CC in a fasting glucose impaired population. The KCNB1 rs1051295 genotype TT in the Chinese Han population is associated with decreased insulin sensitivity and increased plasma TG and W/H ratio, which together contribute to an increased risk for T2D.     

The Association between Two Common Polymorphisms in MicroRNAs and Hepatocellular Carcinoma Risk in Asian Population

Background

Emerging evidence has shown that microRNAs (miRNAs) participate in human carcinogenesis as tumor suppressors or oncogenes. Single nucleotide polymorphism (SNP) located in the miRNAs may influence the function of mature miRNAs and then affect the processing of carcinogenesis. It has been suggested that two common SNPs rs2910164 in miR-146a and rs3746444 in miR-499 are associated with susceptibility to hepatocellular carcinoma (HCC). However, published results are inconsistent and inconclusive. To acquire a more precise effect of the association between these polymorphisms and HCC risk, we performed this meta-analysis.

Methodology/Principal Findings

We have conducted a search of case-control studies on the associations of SNPs rs2910164 and/or rs3746444 with susceptibility to HCC in PubMed, ScienceDirect, Cochrane Central Register of Controlled Trials, and Chinese National Knowledge Infrastructure databases for the period up to Sep 10th, 2012. A total of 6 studies were identified with 2071 cases and 2350 controls for miR-146a rs2910164 polymorphism, 667 cases and 1006 controls for miR-499 rs3746444 polymorphism. It was found that neither allele frequency nor genotype distribution of the two polymorphisms was associated with risk of HCC in all genetic models. Similarly, subgroup analysis in Asian population showed no associations between the two SNPs and the susceptibility to HCC.

Conclusions/Significance

This meta-analysis suggests that miR-146a rs2910164 and miR-499 rs3746444 polymorphisms may not be associated with the risk of HCC, especially for Asian population. However, well-designed studies with larger sample size and more detailed data are needed to confirm these conclusions.     

Association between the Fatty Liver Index and Risk of Type 2 Diabetes in the EPIC-Potsdam Study

The fatty liver index (FLI) predicts fatty liver by using BMI, waist circumference, γ-glutamyltransferase and triglycerides. We investigated the association between the FLI and the risk of type 2 diabetes and evaluated to what extent single FLI components contribute to the diabetes risk. We analysed a case-cohort study (random sub-cohort: 1922; incident cases: 563) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study. The proportion of exposure effect (PEE) explained by single FLI components was evaluated and effect decomposition using inverse probability weighting (IPW) was applied. Women and men with a FLI ≥60 compared to those with a FLI <30 had a multivariable-adjusted Hazard Ratio (HR) of 17.6; 95% confidence interval (CI) 11.1-28.0 and HR: 10.9; 95% CI 6.22-19.2, respectively. Adjustment for BMI or waist circumference attenuated this association in men [PEE_BMI (95% CI) = 53.8% (43.9%-65.8%); PEE_waist (95% CI) = 54.8% (44.2%-68.8%)]. In women, adjustment for waist circumference attenuated the association to a lesser degree than in men [PEE_waist (95% CI) = 31.1%; (21.9%-43.1%)] while BMI had no appreciable effect [PEE_BMI (95% CI) = 11.0% (2.68%-21.0%)]. γ-glutamyltransferase and triglycerides showed only a small attenuation in women [PEE_GGT(95% CI) = 3.11% (-0.72%-4.48%); PEE_TG (95% CI) = 6.36% (3.81%-9.92%)] and in men [PEE_GGT = 0%; PEE_TG (95% CI) = 6.23% (2.03%-11.8%)]. In women, the total effect was decomposed into a direct effect and 4 indirect effects (HR_BMI = 1.10; HR_waist = 1.28; HR_GGT = 0.97 and HR_TG = 1.03). In men, the 4 indirect effects were HR_BMI = 1.25; HR_waist = 1.29; HR_GGT = 0.97 and HR_TG = 0.99. These data suggest that the FLI, as a proxy for fatty liver, is associated with risk of type 2 diabetes. This association is only partly explained by standard estimates of overall and abdominal body fatness, particularly among women.     

Association Analysis between the Polymorphisms of HSD11B1 and H6PD and Risk of Polycystic Ovary Syndrome in Chinese Population

Objectives

To evaluate whether single nucleotide polymorphisms of HSD11B1 (rs846908) and H6PD (rs6688832 and rs17368528) are associated with polycystic ovary syndrome (PCOS) in Chinese population.

Materials and Methods

A case-control study was implemented to investigate the association between HSD11B1 and H6PD polymorphisms and PCOS. Patients with PCOS (n = 335) and controls (n = 354) were recruited in this study. Genetic variants of HSD11B1 (rs846908) and H6PD (rs6688832 and rs17368528) were analyzed by TaqMan method.

Results

We found a significantly 0.79-fold lower risk of G allele of rs6688832 in control group compared with the patients with PCOS (adjusted OR, 0.79; 95%CI = 0.63–0.99; P = 0.040). Additionally, significant difference in the levels of follicle stimulating hormone (FSH) was observed between AA and AG genotype in rs6688832. The rs6688832 AG genotype was associated with lower level of FSH (P = 0.039) and higher risk of hyperandrogenism (P = 0.016) in patients with PCOS. When all subjects were divided into different subgroups according to age and body mass index (BMI), we found that the frequency of G allele of rs6688832 was significantly higher in controls than that in PCOS patients in the subgroup of BMI > 23 (adjusted OR, 0.70; 95% CI = 0.50–0.98; P = 0.037).

Conclusions

Our findings showed a statistical association between H6PD rs6688832 and PCOS risk in Chinese population. The G allele of rs6688832 in H6PD might exert potential genetic protective role against the development of PCOS, especially in overweight women. PCOS patients with AG genotype of rs6688832 might confer risk to the phenotype of hyperandrogenemia of PCOS.     

Association of the Genetic Polymorphisms in Pre-MicroRNAs with Risk of Ischemic Stroke in a Chinese Population

microRNA (miRNA) plays a role in the pathogenesis of ischemic stroke, and single nucleotide polymorphisms in miRNA genes may contribute to disease susceptibility. However, the effect of miR-146a, miR-196a2, and miR-499 polymorphisms on ischemic stroke susceptibility has been rarely reported. Using the TaqMan assay, we evaluated the association of hsa-miR-146a/rs2910164, hsa-miR-196a2/rs11614913, and hsa-miR-499/rs3746444 polymorphisms with the risk of ischemic stroke in a Chinese population with 531 ischemic stroke patients and 531 control subjects. Rs2910164 C/G genotypes were significantly associated with increased risk of ischemic stroke in different genetic model (homozygote comparison: OR = 2.00, 95% CI, 1.29–3.12, P = 0.002; additive model: OR = 1.35, 95% CI, 1.10–1.65, P = 0.004;dominant model: OR = 1.33, 95% CI, 1.00–1.75, P = 0.049; recessive model: OR = 1.82, 95% CI, 1.20–2.74, P = 0.004). Subjects with allele G of hsa-miR-146a/ rs2910164 also showed increased risk of ischemic stroke (OR = 1.33, 95% CI, 1.09–1.62, P = 0.005). Stratification analysis showed that the association between rs2910164 and the risk of ischemic stroke was more pronounced in subjects over 60 years old, females, non-drinkers, subjects without hypertension or diabetes mellitus. There were significant combined effects between miR-146a/rs2910164 and fasting glucose/low-density lipoprotein cholesterol levels on ischemic stroke susceptibility. However, we failed to find any association between the alleles/genotypes of rs11614913 T/C and ischemic stroke, respectively (P> 0.05). In summary, this study provides evidence that miR-146a/rs2910164 might be associated with a significantly increased risk of ischemic stroke in a Chinese population, and the combined effects between miRNA polymorphism and fasting glucose /blood lipid levels may contribute to stroke pathogenesis.