Association of Adiponectin Gene Polymorphisms With the Risk of Coronary Artery Disease in Patients With Nonalcoholic Fatty Liver Disease in a Chinese Han Population.
ABSTRACT: BACKGROUND:Cardiovascular events are an independent risk factor for nonalcoholic fatty liver disease (NAFLD), which is the leading cause of mortality in NAFLD patients. Several recent studies demonstrated that adiponectin (Ad) polymorphisms were involved in the progression of NAFLD and coronary artery disease (CAD). However, reports on the association between Ad polymorphisms and the risk of developing CAD in NAFLD patients are lacking in a Northern Han Chinese population. OBJECTIVES:The present study was designed to evaluate the association between Ad gene polymorphisms (rs266729 and rs2241766) and the risk of developing CAD in Northern Han Chinese patients with NAFLD. MATERIALS AND METHODS:In this case-control study, using the polymerase chain reaction (PCR), Adrs266729 and rs2241766 gene polymorphisms were genotyped in B-type ultrasonography-proven NAFLD patients, with (n = 246) or without (n = 247) CAD and in healthy controls (n = 304). Serum lipid profiles were determined using biochemical methods. Statistical analyses were performed using SPSS 17.0 statistical software. RESULTS:There were significant differences in the Adrs266729 G allele between the NAFLD patients with and without CAD (P < 0.05). In addition, there was a significant difference in the Adrs2241766 G allele of the NAFLD patients compared with that of the controls (P < 0.05). In the NAFLD CAD population, carriers of the G allele of Adrs266729 had higher serum triglycerides (TG), total cholesterol (TC), fasting plasma glucose (FPG), and low-density lipoprotein (LDL) levels and a lower Ad level than their noncarrier counterparts (P = 0.031, P = 0.034, P = 0.007, P < 0.001, and P < 0.001, respectively). NAFLD patients without CAD had higher TG and serum FPG values and a lower Ad level than their noncarrier counterparts (P = 0.014, P = 0.038, and P < 0.001, respectively). In the NAFLD patients with/without CAD, the carriers of the G allele of Adrs2241766 had higher TG levels (P = 0.039 and P = 0.042, respectively) than those of their noncarrier counterparts. CONCLUSIONS:In this Northern Chinese Han population, the Adrs266729 and rs2241766 G alleles were closely associated with the occurrence of NAFLD. However, only NAFLD patients who carried the Adrs266729 G allele had an increased risk of developing CAD.
Project description:Background and Aims: Accumulated studies have evaluated the effects of glucokinase regulatory protein (GCKR) gene polymorphisms on the risk of nonalcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD), but the association of GCKR polymorphisms with the risk of NAFLD and CAD in the Chinese Han population have remained unclear. The aim of this study was to investigate the association between GCKR gene polymorphisms (rs780094 and rs1260326) and the risk of NAFLD and CAD in NAFLD patients in a Chinese Northern Han population. Methods: GCKR rs780094 and rs1260326 gene polymorphisms were genotyped by polymerase chain reaction sequencing for B-type ultrasonography-proven NAFLD patients with (n = 82) or without (n = 142) CAD, and in healthy controls (n = 152). Serum lipid profiles' levels were determined using biochemical methods. Statistical analyses were conducted using SPSS 22.0 statistical software. Results: As the results showed, significant differences in the serum lipid profiles existed between each group. No significant differences were observed in the distributions of genotypes and alleles of GCKR rs780094 and rs1260326 in each group. The GCKR rs780094 T and rs1260326 T allele carriers possessed decreased body mass index value, and serum fasting plasma glucose and TG levels in the overall subjects, respectively. In addition, the GCKR rs780094 T allele carriers possessed decreased serum fasting plasma glucose level in the controls and NAFLD + CAD patients. Conclusions: GCKR rs780094 and rs1260326 polymorphisms were found to be not associated with the risk of NAFLD nor of CAD in NAFLD patients in this Chinese Northern Han population. GCKR rs780094 T and rs1260326 T alleles could affect the body mass index value and serum fasting plasma glucose and triglyceride levels.
Project description:AIMS/INTRODUCTION:The aim of the present study was to examine the associations of rs2241766 (+45T>G), rs1501299 (+276G>T), rs17300539 (-11391G>A) and rs182052 (-10069G>A) in the adiponectin (Ad) gene with adiponectin concentrations, and concomitantly the association of these variants with cardiometabolic risk in type 2 diabetic patients of African ancestry. MATERIALS AND METHODS:A cross-sectional study of 200 patients was carried out. Concentrations of total, high (HMW), middle (MMW) and low (LMW) molecular weight adiponectin isoforms were measured. The four polymorphisms were genotyped. RESULTS:Decreased values were noted for total Ad in overweight, dyslipidemia and coronary artery disease (CAD), for HMW in overweight and dyslipidemia, for MMW in CAD, for LMW in dyslipidemia and CAD, for the percentage HMW/total in overweight, and for MMW:HMW ratio in patients without hypertriglyceridemic waist (HTGW). Significant associations were noted between total Ad, HMW, and HMW/total Ad and rs182052 under a dominant model (P = 0.04, P = 0.03 and P = 0.04, respectively), and between MMW and rs17300539 (P = 0.006). No significant difference in adiponectin concentrations was noted according to rs2241766 and rs1501299 genotypes. Patients carrying the rs2241766 G allele (TG+GG) had an increased risk of HTGW (odds ratio [OR] 3.1; P = 0.04) and of CAD (OR 3.3; P = 0.01). The odds of having low total adiponectin concentrations (<25th percentile: 3.49 ng/mL) for carrying the rs182052A allele (AA+GA) was: OR 0.40; P = 0.009. The single-nucleotide polymorphism associated with adiponectin levels was not concomitantly associated with cardiometabolic risk factors. CONCLUSIONS:Adiponectin concentrations and ADIPOQ variants are implicated in the pathophysiological process leading to cardiovascular diseases, but the genetic effects seem to be independent of adiponectin concentrations in our Afro-Caribbean diabetic patients.
Project description:BACKGROUND: The prevalence of metabolic syndrome has been rising worldwide, including in China, but knowledge on specific genetic determinants of metabolic syndrome is very limited. A number of studies have reported that polymorphisms in the ADIPOQ gene are associated with metabolic syndrome in Chinese Han populations. However, data is still conflicting. The objective of this study was to examine the associations of the adiponectin genetic variants with metabolic syndrome by a case-control study and meta-analyses in Chinese. METHODS: We first investigated the association of ADIPOQ rs2241766 (+45T>G in exon 2), rs266729 (-11377C>G in promoter) and rs1501299 (+276G>T in intron 2) polymorphisms with metabolic syndrome in a Hubei Han Chinese population with 322 metabolic syndrome patients and 161 normal controls recruited from the Yichang, Hubei. Then we comprehensively reviewed the association between ADIPOQ rs2241766/rs266729/rs1501299 and metabolic syndrome in the Chinese populations via a meta-analysis. The strength of association was assessed by odds ratios (ORs) with 95% confidence intervals (CI). RESULTS: The G allele frequency of rs2241766 in metabolic syndrome patients was significantly higher than those of controls group (29.8% vs 23.3%, OR?=?1.40, P?=?0.033). The logistic regression analysis adjusted by gender and age showed a nominally significant association for rs2241766 GG+GT genotype (P?=?0.065, OR?=?1.55) and rs1501299 GG genotype in recessive model (OR?=?1.54, P?=?0.066). However, no association was observed for rs266729 in our sample. We identified thirteen studies for rs2241766 (2,684 metabolic syndrome patients and 2,864 controls), three studies for rs266729, and eleven studies for rs1501299 (2,889 metabolic syndrome patients and 3,304 controls) in Chinese. Meta-analysis indicated significant associations for the rs2241766 G allele (OR?=?1.14, 95%CI?=?1.05-1.24, P?=?0.003), rs266729 GG+GT genotypes (OR?=?0.80, 95%CI?=?0.68-0.92, P?=?0.003) and rs1501299 GG+TG genotypes (OR?=?1.42, 95%CI 1.16-1.75, P?=?0.001). CONCLUSIONS: Our results demonstrated ADIPOQ as a pleiotropic locus for metabolic syndrome and its components in the Han Chinese population.
Project description:Cardiovascular disease (CAD) responsible and nonalcoholic fatty liver disease (NAFLD) are both metabolic diseases, and they are mostly influenced by genetic factors. The aim of our study is to evaluate the relationship between angiotensin II type-1 receptor (AGTR1) gene rs3772622 polymorphisms and the risk of developing coronary artery disease (CAD) in Chinese patients with NAFLD.Genotype for AGTR1 rs3772622 in 574 NAFLD patients with CAD or 589 NAFLD patients without CAD, 332 CAD patients exclude NAFLD and 338 health control subjects were determined by sequencing and polymerase chain reaction analysis. Relevant statistical methods were employed to analyze the genotypes, alleles and the clinical date. Inter-group differences and associations were assessed statistically using t-tests and Chi square and logistic analyses. The relative risk of AGTR1 rs3772622 for NAFLD was estimated by logistic regression analysis.No significant difference in genotype and allele frequency of AGTR1 rs3772622 was found between the NAFLD without CAD population and the controls (P?>?0.05). However, makeable difference was found when compared the CAD in patients with NAFLD and CAD free NAFLD patients (P?<?0.001 OR?=?2.09). Similarly, significant difference was found in AGTR1 rs3772622 genotype distribution between the groups of CAD patients and control (P?=?0.046 OR?=?1.71).AGTR1 rs3772622 gene polymorphism was not associated with the risk of NAFLD, but could increase the risk of NAFLD patients suffering from CAD in the Chinese Han population. Deeply mechanisms underlying the association between AGTR1 rs3772622 gene polymorphism and the risk of CAD in NAFLD patients need more research.
Project description:<b><i>Background and Aims:</i></b> Coronary artery disease (CAD) is a major cause of morbidity and mortality in patients with non-alcoholic fatty liver disease (NAFLD). Previous studies have suggested that <i>TCF7L2</i> rs7903146 was related to the risk of developing NAFLD but the conclusions are not consistent and no related study has been conducted in Chinese populations. The aim of this study was to investigate the association between <i>TCF7L2</i> rs7903146 and the risk of developing NAFLD and CAD in a Chinese Han population. <b><i>Methods:</i></b> <i>TCF7L2</i> rs7903146 genotypes were measured by the MALDI-TOF-MS from 143 NAFLD patients, 159 CAD patients, 131 NAFLD + CAD patients, and 212 healthy controls. The demographic data and serum lipid profiles of all subjects were collected. The distributions of genotype and allele frequency in each group were also tested. Logistic regression was used to investigate the risk of <i>TCF7L2</i> rs7903146 with NAFLD and CAD. All statistical analyses were conducted using SPSS 23.0. <b><i>Results:</i></b> There were no significant differences in the distributions of <i>TCF7L2</i> rs7903146 genotype and allele frequency in each of the two groups, and the <i>TCF7L2</i> rs7903146 CT + TT genotype did not increase the risk of developing NAFLD, CAD, and NAFLD + CAD. Except for body mass index in the control group, the differences of clinical parameters between the <i>TCF7L2</i> rs7903146 T allele carriers and non-carriers in each group were not significant. In the non-obese group, the <i>TCF7L2</i> rs7903146 CT + TT genotype was a protective factor for the development of NAFLD in the non-obese subjects (odds ratio=0.359, 95% confidence interval: 0.134-0.961, <i>p</i> = 0.041). <b><i>Conclusions:</i></b> <i>TCF7L2</i> rs7903146 was not associated with the risk of developing NAFLD, CAD, and NAFLD + CAD in the Chinese Han population. In the non-obese population, the <i>TCF7L2</i> rs7903146 CT + TT genotype was a protective factor against the development of NAFLD.
Project description:ADIPOQ gene polymorphisms were indicated to be associated with coronary artery disease (CAD) in diabetic patients, however, published studies reported inconsistent results. We performed this meta-analysis to reach a more accurate estimation of the relationship between two common ADIPOQ genetic polymorphisms (rs2241766 and rs1501299) and CAD risk in diabetic patients. Eligible studies were retrieved by searching PubMed, Embase, Wangfang, VIP database and China National Knowledge Infrastructure databases. Included and excluded criteria were formulated. The case group was diabetic patients with CAD, and the control group was diabetic subjects without CAD. Summary odds rations (ORs) and 95% confidence intervals (CIs) were used to evaluate ADIPOQ polymorphisms associations with CAD risk in diabetic group. Heterogeneity was evaluated by Q statistic and I2 statistic. A total of twelve published articles, involving 3996 cases and 8876 controls were included in this meta-analysis. The pooled results from rs1501299 polymorphism showed decreased risk in homozygote model (TT VS GG: OR=0.67, 95%CI=0.54-0.83). Heterogeneity was detected in our study. Sensitivity analysis and subgroup analysis were conducted in the meta-analysis. For rs2241766 polymorphism, an increased risk was detected in Caucasian subgroup in heterozygote model (CT VS TT: OR=1.19, 95%CI=1.00-1.42). In genotyping method (PCR-RFLP) subgroup, an increased risk was found in recessive model (GG VS GT+TT: OR=2.05, 95%CI=1.23-3.39). In the sensitivity analysis of rs1501299, decreased risk was detected in allelic model (T VS G: OR=0.86, 95%CI=0.76-0.98) and recessive model (TT VS TG+GG: OR=0.47, 95%CI=0.33-0.67). Publication bias is not observed in our results. Our meta-analysis suggests that the rs1501299 polymorphism may play a protective role in CAD in diabetic patients. The rs2241766 polymorphism is found to be associated with a significant increase in CAD risk in Caucasian and genotyping method (PCR-RFLP) subgroups. Further studies are needed to confirm the prediagnostic effect of the two gene polymorphisms in CAD risk in diabetic patients.
Project description:BACKGROUND:Genome-wide association studies have shown that rs738491, rs2143571, and rs3761472 in the sorting and assembly machinery component 50 homolog (SAMM50) gene are significantly associated with susceptibility to nonalcoholic fatty liver disease (NAFLD). OBJECTIVES:The present study evaluated the association between the three genetic variants in the SAMM50 gene and susceptibility to NAFLD in a Chinese Han population. PATIENTS AND METHODS:Genotypes for 3 single nucleotide polymorphisms (SNPs), viz rs738491, rs2143571, and rs3761472, in the SAMM50 gene were determined using an improved multiplex ligation detection reaction technique in 340 B-type ultrasonography-diagnosed NAFLD patients and 452 healthy controls. Meanwhile, serum lipid profiles and liver enzymes were estimated using standard clinical laboratory methods. The SNP-SNP interactions were analyzed by performing multifactor dimensionality reduction (MDR) and generalized multifactor dimensionality reduction (GMDR). RESULTS:The genotype and allele frequencies of the SAMM50 polymorphisms between the NAFLD group and the control group were significantly different (all Ps < 0.05). In the multivariate analysis adjusted for gender, age, and body mass index, the carriers of the rs738491 T allele, rs2143571 A allele, and rs3761472 G allele had significantly increased susceptibility to NAFLD (OR, 1.507; 95% CI, 1.035 to 2.195; P = 0.032; OR, 1.761; 95% CI, 1.232 to 2.517; P = 0.002; OR, 1.483; 95% CI, 1.039 to 2.115; P = 0.030, respectively). Moreover, the rs738491 T allele carriers had significantly higher levels of alanine aminotransferase (ALT) (P = 0.017) than did the noncarriers. However, differences in the levels of serum triglyceride (TG) and aspartate aminotransferase (AST) were not statistically significant (P = 0.123; P = 0.107). The Rs2143571 A allele and the rs3761472 G allele were both deeply associated with increased levels of serum TG, ALT, and AST (all Ps < 0.05). Furthermore, the MDR and GMDR showed that a synergistic relationship might exist between rs738491, rs2143571, and rs3761472 in the SAMM50 gene and the pathophysiology and genetics of NAFLD. CONCLUSIONS:We first demonstrated that the rs738491 T allele, rs2143571 A allele, and rs3761472 G allele in the SAMM50 gene created susceptibility to NAFLD in a Chinese Han population. The combination of the three SNPs in the SAMM50 gene may have synergism to predict the predisposition to NAFLD.
Project description:Whether adiponectin (ADIPOQ) polymorphisms affect individual susceptibility to coronary artery disease (CAD) remains controversial. Therefore, we performed this meta-analysis to better analyse associations between ADIPOQ polymorphisms and CAD. PubMed, Web of Science, Embase and CNKI were searched for eligible studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Totally, 51 studies were eligible for analyses. In overall analyses, significant associations with the susceptibility to CAD were detected for rs266729 (overdominant model: p= 0.03, OR = 1.11, 95% CI 1.01-1.22), rs822395 (recessive model: p= 0.007, OR = 1.21, 95% CI 1.05-1.40) and rs2241766 (dominant model: p= 0.0009, OR = 0.82, 95% CI 0.73-0.92; recessive model: p= 0.04, OR = 1.29, 95% CI 1.02-1.64; allele model: p< 0.0001, OR = 0.80, 95% CI 0.73-0.88) polymorphisms. Further subgroup analyses by ethnicity revealed that rs1501299 polymorphism was significantly associated with the susceptibility to CAD in East Asians, while rs2241766 polymorphism was significantly associated with the susceptibility to CAD in Caucasians, East Asians and South Asians. In summary, our findings indicated that rs266729, rs822395, rs1501299 and rs2241766 polymorphisms were all significantly associated with the susceptibility to CAD in certain populations.
Project description:Background:Nonalcoholic fatty liver disease (NAFLD) patients are often prone to coronary artery disease (CAD), and CAD is found to be the main cause of death in NAFLD patients. The purpose of this study was to investigate the association between fatty acid desaturase 2 (FADS2) rs3834458 polymorphism and serum FADS2 level with NAFLD and CAD in Chinese Han population. Materials and Methods:The serum level of FADS2 was detected by enzyme-linked immunosorbent assay (ELISA) in healthy people, NAFLD patients, and NAFLD patients combined with CAD (NAFLD+CAD). Polymerase chain reaction (PCR) was used to detect the genotypes of FADS2 rs3834458 in the three groups. Results:Body mass index (BMI), glucose (GLU), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) of the NAFLD group and the NAFLD+CAD group were higher than those of the healthy control group (P < 0.05); the HDL-C of the NAFLD+CAD group was significantly lower than that of the healthy people and the NAFLD group (P < 0.05). The serum FADS2 concentration in the NAFLD+CAD group was significantly higher than that in the NAFLD group (P < 0.05) and the healthy people (P < 0.05). There was no significant difference in genotype distribution (? 2 = 5.347, P < 0.497) and allele frequency (? 2 = 3.322, P = 0.345) between the three groups. Logistic regression analysis showed that the T allele was not an independent risk factor for CAD with NAFLD (OR = 1.62, 95% CI: 0.422-6.180). Conclusions:Serum FADS2 concentration was positively correlated with the susceptibility of NAFLD with CAD, while the polymorphism of rs3834458 was not associated with NAFLD with CAD.
Project description:BACKGROUND:Hyperlipidemia is a major risk factor for coronary artery disease (CAD). As F-box and WD repeat domain-containing 7 (FBXW7) gene is an important regulating factor for lipid metabolism, the aim of the present study is to assess the association between human FBXW7 gene polymorphisms and CAD among Han Chinese and Uygur Chinese populations in Xinjiang, China. METHODS:A total of 1,312 Han Chinese (650 CAD patients and 662 controls) and 834 Uygur Chinese (414 CAD patients and 420 controls) were enrolled in this case-control study. Three single nucleotide polymorphisms (SNPs) rs2255137 T>C, rs2292743 A>T, rs35311955 G>C of FBXW7 were selected and genotyped using the improved multiplex ligase detection reaction (iMLDR) method. RESULTS:We found that the rs2255137 CC genotype was very common in the CAD patients compared with the control subjects in the Uygur Chinese populations. After adjustments for several confounders: age, gender, smoking, drinking, hypertension, diabetes, TG, TC, HDL-C and LDL-C, this association remained significant. Furthermore, we investigated the relationships between rs2255137 genotypes and the circulating serum lipid levels and found that people carrying the C allele of rs2255137 may have higher serum lipid levels in the Uygur Chinese populations. CONCLUSION:Our results indicate that rs2255137 in FBXW7 gene is associated with CAD in the Uygur Chinese population in China.