The influence of the adiponectin gene on adiponectin concentrations and parameters of metabolic syndrome in non-diabetic Korean women

BACKGROUND: Concentrations of adiponectin, the protein product of the adipocyte C1q and collagen-domain-containing (ADIPOQ) gene are associated with type 2 diabetes and coronary artery disease. We investigate the association of single-nucleotide polymorphisms (SNPs) in the ADIPOQ gene with adiponectin concentrations, and to parameters of metabolic syndrome. METHODS: 867 unrelated, non-diabetic Korean women, 20 to 69 y, were genotyped for 8 SNPs in the ADIPOQ gene (-11391G>A, -11377C>G, H241P, Y111H, G90S, R221S, 45T>G, 276G>T). Adiponectin, a homeostasis model assessment of insulin resistance (HOMA-IR), and metabolic parameters were measured. RESULTS: Carriers of genotype T/T at position 276 had significantly higher adiponectin concentrations than G/G carriers (P=0.005). Homozygous carriers of the TG haplotype (i.e., individuals who were T/T at 45 and G/G at 276) and heterozygous carriers of the TG haplotype (TG/X) had lower adiponectin concentrations than non-TG carriers (P<0.001). Significant associations between SNP at 276 and serum concentrations of triglyceride (P=0.013), insulin (P=0.013) and HOMA-IR (P=0.012) were found. The 45-276 haplotypes had associations identical to the 276G>T SNP. In subgroup analysis, subjects carrying the TG haplotype had significantly lower adiponectin concentrations than non-TG carriers in both normal weight (P<0.001) and overweight-obese (P=0.009) subgroups. The association of the TG haplotype with increasing insulin concentrations was significant among overweight-obese subjects (P=0.004), but was not significant among normal weight subjects. A similar association was found between the 45-276 haplotype and HOMA-IR. CONCLUSION: There is a strong association of the adiponectin SNP276 genotypes and the adiponectin 45-276 haplotypes with circulating adiponectin concentrations in non-diabetic Korean women. In addition, this haplotype is associated with increased insulin concentrations and insulin resistance index only in overweight-obese individuals.     

大理白族2型糖尿病与脂联素基因多态性相关性分析

目的检测云南省大理白族脂联素基因启动子单核苷酸多态性（SNP）与2型糖尿病的相关性。方法采用聚合酶链反应直接测序法在300例无血缘关系的云南省大理白族人群（健康者120例,2型糖尿病患者180倒）中检测SNPs＋45、＋276的基因型,分析以上2个多态性位点与2型糖尿病的相关性。结果sNP＋45位点在健康者和2型糖尿病患者具有明显差异,SNP＋276在两组差异无统计学意义。连锁不平衡分析显示,健康组和病例组间SNPs＋45、＋276存在一定差异。结论大理白族人群脂联素基因上sNP＋45G与2型糖尿病的发生存在关联;SNP＋45G是2型糖尿病发生的一项危险因素。     

Associations between single-nucleotide polymorphisms of the adiponectin gene,serum adiponectin levels and increased risk of type 2 diabetes mellitus in Iranian obese individuals

Abstract

Introduction: Adiponectin is an adipose tissue-secreted hormone with important metabolic effects. There have been inconsistent reports about SNPs of the adiponectin gene and risk of type 2 diabetes (T2DM). The aim of this study was to investigate any association between SNPs (+45 T/G and +276 G/T) of the adiponectin gene with serum adiponectin levels, metabolic factors and risk of T2DM in obese individuals. Design and methods: Genotyping for two common SNPs of adiponectin gene was performed in 50 unrelated obese type 2 diabetic patients and 52 obese non-diabetic control subjects by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Lipid profile was measured by enzymatic methods. Serum adiponectin, insulin, leptin and glucose levels were measured by immunoassay, and glucose oxidase methods, respectively. Results and conclusion: It was observed that obesity and T2DM are associated with low serum adiponectin levels. The G allele and TG/GG genotype of SNP 45 occurred more frequently than the T allele and TT genotype in T2DM patients compare to the controls (p<0.05). Subjects with the G/G + TG genotype of SNP 45 were at increased risk for T2DM [Odds Ratio (OR) 2.574; 95% Confidence Interval (CI) 1.051–6.302; p=0.036] compared with those T/T genotype. There was no statistically significant difference in allele and genotype frequencies of SNP 276 comparing control group with T2DM group. Thus, our results demonstrated that, adiponectin SNP 45T/G, rather than SNP 276G/T, is more associated with risk of T2DM in obese individuals.     

Contribution of adiponectin polymorphisms to the risk of coronary artery disease in a North‐African Tunisian population

Background

Adiponectin, an adipocyte‐derived protein, is known to play a key role in the processes leading to atherosclerosis and coronary artery disease (CAD) through its anti‐atherogenic, anti‐inflammatory, antioxidative, and anti‐apoptotic properties. In the current study, we have studied the association of two single nucleotide polymorphisms (SNPs) +45 T>G (rs2241766) and +276 G>T (rs1501299) of the adiponectin gene with coronary artery disease (CAD) on an Arab/North‐African population from Tunisia.

Methods

Subjects comprised 277 patients with angiographically demonstrated CAD and 269 age‐ and gender‐matched control subjects. The adiponectin genotypes were performed by polymerase chain reaction‐restriction fragment length polymorphism analysis (PCR‐RFLP). The contribution of adiponectin variants to CAD was analyzed by haplotype and regression analysis.

Results

Adiponectin +45T>G and +276G>T genotypic and allelic distributions did not show a significant difference between cases and controls. Similarly, no association with CAD was observed for the haplotype analysis. Assuming dominant model of transmission for both polymorphisms and after adjustment of a number of traditional risk factors for CAD, logistic regression analysis showed an association of SNP +45 T>G with increased risk of developing CAD [adjusted OR (95% CI) = 2.59 (1.17‐5.70); P = .01]. However, SNP + 276 G>T is associated with decreased risk of developing CAD [adjusted OR (95% CI) = 0.47 (0.22‐0.97); P = .04].

Conclusion

There is no allelic or genotypic association of +45 T>G and +276 G>T of the adiponectin gene with CAD in the Tunisian population.

     

2型糖尿病及合并冠心病糖尿病患者脂联素水平观察

目的：观察脂联索(adiponectin)在2型糖尿病(DM)及DM合并冠心病时的浓度变化．并探讨影响2型糖尿病患血浆脂联索水平的因素。方法：用ELISA方法在2型糖尿病组(无或合并冠心病)、非糖尿病正常对照组测定血浆脂联索水平。结果：无冠心病的糖尿病组血浆脂联索水平较非糖尿病正常对照组明显降低．合并冠心病的糖尿病组更低。结论：2型糖尿病中血浆脂联索水平的明显下降可作为冠心病的危险标志。     

Effect of adiponectin gene polymorphisms on circulating adiponectin and insulin resistance indexes in women with polycystic ovary syndrome

BACKGROUND: We examined the possible association of adiponectin gene polymorphisms with polycystic ovary syndrome (PCOS) and their influence on serum adiponectin and insulin resistance indexes in Greek women with PCOS. METHODS: We genotyped samples from 100 women with PCOS characterized with respect to body mass index (BMI), glucose and insulin concentrations during an oral glucose tolerance test (OGTT), lipid profile, and serum adiponectin concentrations and from 140 healthy controls for the 45T>G and 276G>T polymorphisms in the adiponectin gene. RESULTS: The distributions of genotypes and alleles of both polymorphisms were no different in women with PCOS and controls, indicating that the individual polymorphisms are not associated with increased risk for PCOS. However, the two polymorphisms were found to be associated with insulin resistance indexes among women with PCOS and to influence adiponectin production. In particular, carriers of the TG genotype at position +45 had greater hyperinsulinemia, as estimated by the area under the curve for insulin (AUC(insulin)) during the OGTT, than those with the TT genotype (P <0.05), and this was independent of age and BMI. In addition, women with PCOS with the GG or GT genotypes at position +276 had a higher BMI (P = 0.01) and greater AUC(insulin) (P = 0.01) than carriers of the TT genotype. The latter genotype was found less frequently among overweight/obese women with PCOS than in normal-weight individuals (P = 0.002). In addition, the presence of the GG or GT genotype was associated with lower serum adiponectin than the TT genotype, independent of age, BMI, and insulin concentrations (P = 0.03). Serum adiponectin was negatively correlated with serum triglycerides and insulin resistance indexes and positively with HDL-cholesterol. CONCLUSIONS: Adiponectin gene polymorphisms at positions +45 and +276 are not associated with PCOS. However, these genomic variants may influence production of adiponectin and the metabolic variables related to insulin resistance/metabolic syndrome in patients with PCOS.     

The influence of adiponectin gene polymorphism on the rosiglitazone response in patients with type 2 diabetes

OBJECTIVE: The aim of this study was to examine the effects of rosiglitazone on adiponectin and plasma glucose levels in relation with common adiponectin gene (ACDC) polymorphisms. RESEARCH DESIGN AND METHODS: A total of 166 patients with type 2 diabetes were treated with rosiglitazone (4 mg/day) for 12 weeks without changing any of their previous medications. In all, single nucleotide polymorphism (SNP)45 and SNP276 of ACDC were examined. RESULTS: Regarding SNP45, there was a smaller reduction in the fasting plasma glucose (FPG) level and the HbA(1c) value in the carriers of the GG genotype than in the carriers of the other genotypes (P = 0.031 and 0.013, respectively). There was a smaller increase in the serum adiponectin concentration for the GG genotype than for the other genotypes (P = 0.003). Regarding SNP276, there was less reduction in the FPG level for the GG genotype than for the other genotypes (P = 0.001). In the haplotype analysis, the reductions in the FPG and HbA(1c) levels were smaller for the GG homozygote haplotype than for the other haplotypes (P = 0.001 and 0.001, respectively). The increase in the plasma adiponectin concentration for the GG homozygote haplotype was smaller than that of the other haplotypes (P = 0.003). CONCLUSIONS: These data suggest that genetic variations in the adiponectin gene can affect the rosiglitazone treatment response of the circulating adiponectin level and blood glucose control in type 2 diabetic patients.     

Silent myocardial ischemia in patients with diabetes: who to screen.

OBJECTIVE: Silent myocardial ischemia (SMI) is more common in diabetic patients than in the general population. However, the exact prevalence of SMI is not known, and routine screening is costly. The purpose of this 1-year study was to estimate the prevalence of SMI and define a high-risk diabetic population by systematically testing patients with no symptoms of coronary artery disease (CAD). RESEARCH DESIGN AND METHODS: The criteria for inclusion in this study were age (between 25 and 75 years), duration of diabetes (>15 years for type 1 diabetes, 10 years for type 2 diabetes with no cardiovascular risk factors, and 5 years for type 2 diabetes with at least one cardiovascular risk factor), and absence of clinical or electrocardiogram (ECG) symptoms of CAD. For 1 year, 203 patients were screened, including 28 women and 45 men with type 1 diabetes (aged 41.5+/-10.9 years, mean duration of diabetes 20.9+/-7.7 years [mean +/- SD]) and 61 women and 69 men with type 2 diabetes (aged 60.7+/-8.7 years, duration of diabetes 16.5+/-7.1 years). Exercise ECG was the first choice for screening method. If exercise ECG was not possible or inconclusive, thallium myocardial scintigraphy (TMS) with exercise testing and/or dipyridamole injection was performed. If any one of these tests was positive, coronary angiography was carried out and was considered to be positive with a stenosis of > or =50%. RESULTS: Positive screening results were obtained in 32 patients (15.7%). Coronary angiography demonstrated significant lesions in 19 patients (9.3%) and nonsignificant lesions in 7 patients (1 false-positive result for exercise ECG and 6 false-positive results for TMS). Coronary angiography was not performed in six patients. All but 3 of the 19 patients (15 men and 4 women) in whom silent coronary lesions were detected presented with type 2 diabetes. The main differences between the 16 type 2 diabetic patients presenting with coronary lesions and the type 2 diabetic patients without SMI were a higher prevalence of peripheral macroangiopathy (56.2 vs. 15.1%, respectively, P < 0.01) and a higher prevalence of retinopathy (P < 0.05). No correlation was found between SMI and duration of diabetes, HbA1c level, renal status, or cardiovascular risk factors except for family history of CAD. CONCLUSIONS: The results of this study allowed us to determine a high-risk group for SMI in the diabetic population. SMI with significant lesions occurs in 20.9% of type 2 diabetic male patients who are totally asymptomatic for CAD. Based on these findings, we recommend routine screening for male patients in whom the duration of type 2 diabetes is >10 years or even less when more than one cardiovascular risk factor is present.     

Low serum adiponectin is independently associated with both the metabolic syndrome and angiographically determined coronary atherosclerosis

BACKGROUND: We aimed at investigating serum adiponectin in patients with the metabolic syndrome (MetS), in patients with angiographically diagnosed coronary artery disease (CAD), and in patients who had both, the MetS and CAD. METHODS: We enrolled 687 consecutive patients undergoing coronary angiography for the evaluation of CAD. RESULTS: From our patients, 178 had neither the MetS (Adult Treatment Panel III definition) nor significant CAD (MetS-/CAD-), 91 had the MetS, but not significant CAD (MetS+/CAD-), 251 did not have the MetS but had significant CAD (MetS-/CAD+), and 167 had both, the MetS and significant CAD (MetS+/CAD+). Serum adiponectin was highest (12.1+/-8.3 microg/ml) in MetS-/CAD- subjects. It was significantly lower in MetS+/CAD- (9.5+/-7.3 microg/ml; p=0.001) and in MetS-/CAD+ patients (9.2+/-5.3 microg/ml; p<0.001) and lowest in MetS+/CAD+ patients (6.7+/-3.8 microg/ml) in whom it was significantly lower than in MetS-/CAD-, MetS+/CAD-, and MetS-/CAD+ patients (p<0.001 for all comparisons). In analysis of covariance the MetS and significant CAD proved associated with serum adiponectin in a mutually independent manner. CONCLUSIONS: Low serum adiponectin is independently associated with both the MetS and coronary atherosclerosis.     

Butyrylcholinesterase K variants increase the risk of coronary artery disease in the population of western Iran

The conflicting results of several studies suggest that there is an association between the butyrylcholinesterase-K variant (BCHE-K, G1615A/Ala539Thr) and the risk of developing coronary artery disease (CAD) in diabetes and non-diabetic subjects. The objective of this study was to determine whether the presence of the BCHE-K variant exacerbates the risk of CAD in patients from western Iran with and without type 2 diabetes mellitus (T2DM). This case-control study comprised 464 subjects undergoing their first coronary angiography. They were matched and randomly assigned into four groups: CAD+T2DM+ (CAD/T2DM), CAD+DM(-) (CAD/ND), CAD(-)DM+ (T2DM/NCAD) and CAD(-)DM(-)(control). The BCHE-K variant was detected by PCR-RFLP. The BCHE-K allele frequency in CAD patients with and without T2DM [total CAD (TCAD)] and separately for each group (CAD/T2DM and CAD/ND) was significantly higher than in the control group (21.1 % versus 13.3 % (p = 0.001), 22.4 % versus 13.3 % (p = 0.001) and 19.7 % versus 13.3 % (p = 0.015), respectively). The odds ratios (ORs) for the BCHE-K heterozygous and homozygous variants in TCAD subjects were 1.65 (95 % CI 1.17-2.3; p = 0.004) and 4.3 (1.05-19.4; p = 0.048); for CAD/T2DM individuals 1.76 (1.2-2.6; p = 0.004) and 4.73 (0.96-23.3; p = 0.052); and for CAD/ND patients 1.53 (1.05-2.3; p = 0.029) and 3.88 (0.8-19.7; p = 0.7), respectively. The OR of the BCHE-K allele was found to be 1.74 (1.1-2.4; p = 0.001) in TCAD subjects, 1.87 (1.12-1.48; p = 0.001) in the CAD/T2DM group and 1.59 (1.04-1.4; p = 0.016) in CAD/ND subjects. These data suggest that the BCHE-K allele increases the risk of CAD in the population (with and without DM) in western parts of Iran, and its presence intensifies the risk of CAD in T2DM. The fact that the BCHE-K allele, even in the heterozygous form, exacerbates the risk of CAD in this population, suggests that a specific therapeutic intervention should be considered for this particular group of patients.     

The presence of apolipoprotein epsilon4 and epsilon2 alleles augments the risk of coronary artery disease in type 2 diabetic patients

OBJECTIVE: It has been suggested that there is a relationship between apolipoprotein E polymorphism and the severity of coronary artery disease in type II diabetes mellitus (T2DM). The current study specifically aimed to examine whether APOE polymorphism in association with serum lipids-lipoproteins level is a risk factor for developing coronary artery disease (CAD) in diabetic patients living in western of Iran. METHODS: The APOE genotypes were detected by PCR-RFLP in 152 angiographically documented diabetic CAD patients, 262 non-diabetic (ND) individuals with CAD and 300 unrelated controls (normal coronary artery cases without diabetes) and serum lipid level was measured enzymatically. RESULTS: The APOE-epsilon4 and epsilon2 allele frequencies were significantly higher in the CAD/T2DM and CAD/ND patients than in the control group (p<0.001). Our study demonstrated a significant association between APOE polymorphism and the level of plasma lipids with CAD/T2DM (p=0.001) and CAD/ND (p=0.026) patients. The CAD subjects with T2DM and ND patients carrying APOE-epsilon4 allele had lower plasma HDL-C level (p<0.001), (p=0.008) but had higher plasma LDL-C (p=0.01), total cholesterol (p=0.002), (p=0.03) and TG (p<0.001), (p=0.042) than that of the APOE-epsilon3 carriers, respectively. However, carriers of APOE-epsilon2 had significantly higher levels of plasma TG only. OR of APOE-epsilon4 and epsilon2 alleles in CAD/T2DM and CAD/ND patients were found to be 2.98 (p=0.001),1.86 (p=0.001), 2 (p=0.001), and 1.65 (p=0.001), respectively. CONCLUSIONS: The major finding of the present case-control study is that T2DM patients carrying APOE-epsilon2 and epsilon4 alleles have a higher risk of developing CAD than ND patients in the western population of Iran, with APOE-epsilon4 being more closely associated with CAD than the APOE-epsilon2 allele. These results indicated that carriers of APOE-epsilon4 allele have a distinct plasma lipids profile and carrier of this allele with low levels of HDL-C and with high levels of LDL-C may be susceptible to CAD and myocardial infarction specially in diabetic patients. This suggests that a therapeutic modality should be considered for these patients.     

Osteoprotegerin is associated with silent coronary artery disease in high-risk but asymptomatic type 2 diabetic patients

OBJECTIVE: Osteoprotegerin (OPG) is an inhibitor of osteoclastogenesis, which has been recently involved in atherosclerosis. The relationship between coronary atherosclerosis and OPG has never been studied in asymptomatic type 2 diabetic patients. RESEARCH DESIGN AND METHODS: This is a nested case-control study; 162 asymptomatic type 2 diabetic patients were evaluated for silent myocardial ischemia using stress myocardial perfusion imaging; of 50 patients with positive results, 37 underwent coronary angiography, 20 of whom showed significant coronary artery disease (CAD group). Of 112 patients without silent myocardial ischemia, 20 subjects (NO-CAD group) were selected and matched by age and sex to patients with CAD. OPG, C-reactive protein, adiponectin, lipoprotein(a), albuminuria, and classical risk factors were measured. RESULTS: The percentages of subjects with OPG levels above median and with nephropathy were higher in the CAD group than in the NO-CAD group (70 vs. 25%, P = 0.004 and 50 vs. 5%, P = 0.001, respectively). LDL cholesterol levels were higher and HDL cholesterol levels lower in the CAD compared with the NO-CAD group (P = 0.033 and P = 0.005, respectively). No other variables were associated with CAD. Logistic regression analysis showed that OPG values above median (odds ratio 8.31 [95% CI 1.18-58.68], P = 0.034) and nephropathy (21.98 [1.24-388.36], P = 0.035) were significant independent predictors of asymptomatic CAD in type 2 diabetic patients. CONCLUSIONS: Our investigation reports the first evidence of an independent association of OPG with asymptomatic CAD in type 2 diabetic patients. The results of this nested case- control study with 20 cases need to be confirmed in a larger population.     

Assessment of asymptomatic coronary artery disease in apparently uncomplicated type 2 diabetic patients: a role for lipoprotein(a) and apolipoprotein(a) polymorphism

OBJECTIVE: In patients with uncomplicated diabetes, there is low probability of finding significant coronary artery disease (CAD) by noninvasive tests. Therefore, screening for its presence is not justified, and it is important to find reliable predictors of silent CAD to identify patients with uncomplicated diabetes for further screening. The relationship between lipoprotein(a) [Lp(a)], apolipoprotein(a) [apo(a)] polymorphism, and silent CAD has never been studied. We investigated the association of Lp(a) and apo(a) polymorphism with angiographically documented asymptomatic CAD in type 2 diabetic patients without evident complications. RESEARCH DESIGN AND METHODS: A total of 1,323 diabetic patients without any clinical and electrocardiographic evidence of CAD were evaluated. Of 121 patients with highly positive results of exercise electrocardiography (ECG) (n = 30) or positive results on exercise thallium scintigraphy (n = 91), 103 subjects showed angiographically documented CAD (CAD group). Of 1,106 patients with negative results on exercise ECG, 103 subjects without CAD (NO CAD group) were selected and matched by age, gender, and duration of diabetes to patients in the CAD group. In patients in the NO CAD group, results of exercise ECG, 48-h ambulatory ECG, and stress echocardiography were negative for CAD. RESULTS: The CAD group had higher Lp(a) levels (21.7 +/- 17.7 vs. 15.2 +/- 19.0 mg/dl; P = 0.0093) than the NO CAD group, and a percentage of subjects had at least one small apo(a) isoform (68.9 vs. 29.1%; P = 0.0000) higher than the NO CAD group. Logistic regression analysis showed that apo(a) phenotypes (odds ratio [OR] 8.13, 95% CI 3.65-21.23), microalbuminuria (5.38, 2.44-11.88), smoking (2.72, 1.31-5.64), and Lp(a) levels (2.41, 1.15-5.03) were predictors of asymptomatic CAD. CONCLUSIONS: Our investigation reports the first evidence of an independent association of Lp(a) and apo(a) polymorphism with asymptomatic CAD. This suggests that Lp(a) levels and apo(a) phenotypes could be used together with other risk factors as markers of asymptomatic CAD in patients with diabetes.     

Different susceptibility to insulin resistance and fatty liver depending on the combination of TNF-α C-857T and adiponectin G+276T gene polymorphisms in Japanese subjects with type 2 diabetes

The C-857T promoter polymorphism of TNF-α gene is associated with obese type 2 diabetes, while the adiponectin G+276T gene polymorphism in intron 2 may influence the fat accumulation in the liver. In this study, we examined effects of these polymorphisms on clinical markers of insulin resistance and fatty liver (a liver/spleen CT ratio < 0.9). These polymorphisms were determined in 342 Japanese subjects with type 2 diabetes. The liver/spleen CT ratio was lower in the subjects with the adiponectin +276G/G genotype than that in the subjects with the +276T allele (P < 0.05), indicating that fat accumulation in the liver is associated with the +276G/G genotype. Multiple comparisons among the 4 combinations of each polymorphism of the TNF-α and adiponectin genes revealed a significant difference in the liver/spleen CT ratio (P < 0.05) among the 4 groups, indicating that the gene combinations influence the degree of fat accumulation in the liver. The subjects carrying the TNF-α -857T allele (C/T or T/T genotype) and the adiponectin +276G/G genotype had greater risks for fatty liver and insulin resistance that was evaluated by higher levels of fasting insulin and homeostasis model assessment of insulin resistance, as compared with the other groups. Therefore, Japanese subjects with the TNF-α -857T allele and the adiponectin +276G/G genotype may be more susceptible to insulin resistance and fatty liver. The present study provides the evidence for the interaction between TNF-α and adiponectin genes in the insulin resistance and fatty liver in Japanese subjects with type 2 diabetes.     

Functional vascular endothelial growth factor -634G>C SNP is associated with proliferative diabetic retinopathy: a case-control study in a Brazilian population of European ancestry

OBJECTIVE: The purpose of this study was to evaluate the effect of the single nucleotide polymorphism (SNP) -634G>C at the 5' regulatory region of the vascular endothelial growth factor (VEGF) in the risk of proliferative diabetic retinopathy (PDR) in the Brazilian population of European ancestry with type 2 diabetes. RESEARCH DESIGN AND METHODS: A case-control study was conducted in 501 type 2 diabetic patients of European ancestry. Patients underwent a standardized clinical, ophthalmological, and laboratory evaluation. Of these, 167 patients had PDR (case patients), and 334 were considered as control subjects (patients without PDR) for PDR. A reference population (110 individuals of European ancestry) was also evaluated. RESULTS: No evidence of association between -634G>C/VEGF and the presence of diabetic retinopathy or type 2 diabetes was observed (P > 0.05). However, CC homozygous for the SNP -634G>C was significantly more frequent in patients with PDR (37 of 167; 22.2%) than in the corresponding control group (40 of 334; 12%) in accordance with a recessive model (P = 0.003). This effect was further observed when creatinine, BMI, sex, duration of type 2 diabetes, HDL cholesterol, and systolic blood pressure were taken into account (odds ratio 1.9 [95% CI 1.01-3.79], P = 0.04). CONCLUSIONS: The presence of the allele -634C/VEGF in homozygosity is an independent risk factor for the development of PDR in type 2 diabetic patients of European ancestry.     

Association between the eNOS (Glu298Asp) and the RAS genes polymorphisms and premature coronary artery disease in a Turkish population

BACKGROUND: The renin-angiotensin system (RAS) and endothelial nitric oxide (NO) affect the pathogenesis of atherosclerosis and prognosis of coronary artery disease (CAD). Previous epidemiologic data suggested that genetic factors are more likely to affect young rather than old people. Our objective was to investigate the association between the polymorphisms of eNOS (Glu298Asp) and the RAS genes and premature CAD in a Turkish population. METHODS: A total of 115 Turkish patients with premature CAD and 83 controls were included in the study. ACE I/D, AT1R A/C, AGT T/M and eNOS Glu298Asp gene polymorphisms were analysed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULTS: It was found that increased premature CAD risk is associated with higher frequencies of the ACE DD [OR: 2.600 (CI 95% 1.395-4.847, p=0.002)], AGT MM [OR=2.407 (CI 95% 1.267-4.573, p=0.007)] and eNOS 894TT [OR=17.000 (CI 95% 3.952-73.125, p<0.001)] genotypes. Carriers of ACE DD+eNOS 894TT (p=0.002), AGT MM+eNOS 894TT (p=0.001), AT1R AA+eNOS 894TT and AT1R non-AA+eNOS 894TT (p=0.002) genotypes were significantly associated with the risk of premature CAD. CONCLUSIONS: This study indicates a synergistic contribution of RAS genes (ACE I/D, AGT T/M, AT1R T/C) and eNOS Glu298Asp polymorphisms to the development of the premature CAD.     

Genetic association study of APOA1/C3/A4/A5 gene cluster and haplotypes on triglyceride and HDL cholesterol in a community-based population

BACKGROUND: Polymorphism of apolipoprotein A1/C3/A4/A5 gene cluster affected lipid profiles in general population. We reported 6 polymorphisms, APOA1 -75G>A, APOA1 83C>T, APOC3 3175C>G, APOC3 3206G>T, APOA4 127A>G, and APOA5 553G>T in APOA1/C3/A4/A5 gene and the haplotype structures on triglyceride and HDL traits among ethnic Chinese. RESULTS: Overall, there were statistically significant differences in the distribution of APOA1 -75G>A and APOA5 +553G>T genotypes comparing cases with control subjects. For the APOA1 -75 SNP, a lower risk of triglyceride/HDL among subjects with A/A genotype compared with those with the G/G genotype (odds ratio, OR=0.39, 95% CI 0.16-0.92, P=0.04). However, the risk magnitude reduced after multivariate adjustments. For continuous traits, we found that only in APOA5 +553 T allele carriers showed a significant higher triglyceride and a significant lower HDL cholesterol level than subjects with APOA5 +553 G/G genotypes. There were significant differences in overall haplotype frequencies between case and control subjects (P<0.001). CONCLUSION: There is an important role of APOA1/C3/A4/A5 gene polymorphisms and haplotypes in the development of high triglyceride/HDL ratio in Chinese.     

中国人群脂联素基因+276G/T位点多态性与T2DM易感性的Meta分析

目的 探讨中国人群脂联素基因+276G/T位点多态性与2型糖尿病(T2DM)的相关性.方法 检索2011年8月前中国知网、维普中文科技期刊全文数据库、中国万方数据库、中国学位论文全文数据库和中国重要会议论文全文数据库及Medline、Cochrane Library、Embase、Springer、Ovid等数据库,收集有关中国人群脂联素基因+276G/T位点多态性与T2DM相关性研究的文献;评价纳入研究质量,提取有效数据,采用Review Manager 5.0软件进行Meta分析.结果 共纳入11项研究中国人群脂联素基因+276G/T位点多态性与T2DM相关性的病例对照研究;T2DM患者1 697例,健康对照者1 341例.Meta分析结果显示,脂联素基因+276G/T位点G/T多态性与T2DM的相关性中T等位基因与G等位基因(OR=0.83,95% CI为0.65～1.05,P=0.12)、基因型(GT+TT)与GG(OR=0.82,95% CI为0.60～1.12,P=0.20)、基因型GT与GG(OR=0.93,95%CI为0.63～1.38,P=0.72)、基因型TT与GG(OR=0.81,95%CI为0.46～1.42,P=0.46)比较,差异均无统计学意义.结论 中国人群脂联素基因+276G/T位点多态性可能与T2DM易感性无关.     

Interaction of the -308G/A promoter polymorphism of the tumor necrosis factor-alpha gene with single-nucleotide polymorphism 45 of the adiponectin gene: effect on serum adiponectin concentrations in a Spanish population

BACKGROUND: We investigated whether interactions of the -308G/A polymorphism in the promoter region of the tumor necrosis factor-alpha (TNF-alpha) gene with single-nucleotide polymorphisms (SNPs) 45 and 276 of the adiponectin gene are associated with circulating adiponectin and soluble TNF-alpha receptor 2 (sTNFR2) concentrations in a Spanish population. METHODS: We performed anthropometric and physiologic measurements in 809 unrelated participants recruited with a simple random sampling approach from respondents to a cross-sectional population-based epidemiologic survey in the province of Segovia in central Spain (Castille). RESULTS: The 2-h postload glucose and serum insulin concentrations were higher in -308A allele carriers than in -308G/G individuals homozygous for the TNF-alpha gene. Plasma concentrations of sTNFR2 were positively correlated with body mass index, waist-to-hip ratio, and sagittal abdominal diameter among individuals with type 2 diabetes. Individuals with type 2 diabetes and the -308A allele had higher sTNFR2 and lower adiponectin concentrations than -308G homozygotes. Moreover, individuals carrying both the TNF-alpha -308A allele and the G allele of SNP 45 in the adiponectin gene had the highest prevalence of impaired glucose tolerance (adjusted odds ratio, 1.26; 95% confidence interval, 1.01-1.56; P = 0.038) and had lower adiponectin concentrations (beta = -0.090; P = 0.005) than individuals without these genotypes. CONCLUSIONS: Our findings are the first to indicate that a higher incidence of impaired glucose tolerance and low circulating adiponectin concentration may be associated with interaction between the -308G/A promoter polymorphism of the TNF-alpha gene and SNP 45 in the adiponectin gene.