Endothelial nitric oxide synthase gene haplotypes and diabetic nephropathy among Asian Indians

Endothelial dysfunction plays a key role in the pathogenesis of diabetic vascular disease, including diabetic nephropathy. Endothelial-derived nitric oxide synthase (eNOS) gene polymorphisms affect eNOS activity and are associated with endothelial dysfunction. We evaluated the association of the constitutive endothelial nitric oxide synthase gene (eNOS) polymorphisms with type 2 diabetic nephropathy. We genotyped three polymorphisms of eNOS (Two SNPs: -786T > C, 894G > T and one 27-bp repeat polymorphism in Intron 4 (27VNTR)) in type 2 diabetic nephropathy patients (cases: n = 195) and type 2 diabetic without nephropathy (controls: n = 255), using validated PCR-RFLP assays. We measured serum NO levels in these subjects and examined its correlation with diabetic nephropathy and eNOS genotypes. The frequency of CC (-786T > C), TT (894G > T) and aa genotypes (27VNTR) were significantly higher in diabetic nephropathy patients as compared to the diabetes without nephropathy group (CC: P = 0.003, TT: P = 0.03, aa: P < 0.0001). These mutant genotypes were found to be associated with higher risk of nephropathy (-786T > C: OR: 5.5, 95%CI: 1.53-19.79; 894G > T: OR: 1.8, 95%CI: 1.03-3.16; Intron 4: OR: 6.23, 95%CI: 2.23-16.31). Haplotype with all the wild alleles (T-b-G) was found to be associated with a decreased risk of nephropathy (OR: 0.68, P = 0.005) and haplotype with all mutant alleles (C-a-T) was associated with higher risk of diabetic nephropathy as compared to diabetes without nephropathy group (OR: 2.6, P = 0.14). No significant linkage disequilibria were observed among the variants in this case-control study. The serum NO levels were observed to be significantly (P < 0.05) lower in mutant allele carriers ('C' allele of T-786C SNP and/or 'T' allele of G894T SNP) as compared with the wild-type allele carriers (-786T and/or 894G) within each of the subject groups (with and without nephropathy). These results suggest that the eNOS gene locus is associated with diabetic nephropathy and the functional polymorphisms (-786T > C & 894G > T) might lead to a decreased expression of eNOS gene.     

eNOS 894T allele and coronary blood flow at rest and during adenosine-induced hyperemia

The 894T allele of a G894T polymorphism in the endothelial nitric oxide synthase (eNOS) gene is associated with decreased eNOS activity, cleavage of the protein, and endothelial dysfunction. The present study evaluated the association with coronary blood flow (CBF) at rest and during adenosine (ADO)-induced hyperemia. CBF was determined by Doppler flow wire and angiography in 97 left anterior descending arteries of individuals without coronary artery disease. At rest, average peak velocity (APV) was lower and coronary vascular resistance (CVR) was higher in homozygous carriers of the 894T allele than in heterozygotes and individuals without the 894T allele. CBF tended to be lower in eNOS 894T allele carriers. During ADO-induced hyperemia (18 microg ic), APV, CVR, and CBF were not statistically different between the genotypes. The reduced APV at rest in conjunction with an increased CVR indicates a vasomotor dysfunction related to an increased microvascular resting tone in eNOS 894T allele carriers.     

Polymorphism in exon 7 of the endothelial nitric oxide synthase gene is associated with low incidence of microvascular damage in type 1 diabetic neuropathy

Microvascular complications associated with type 1 diabetes mellitus (T1DM) are caused in part by endothelial dysfunction. We aimed to determine the association between polymorphisms in endothelial nitric oxide synthase (eNOS) gene (894G>T, 4ab) and T1DM-associated microvascular disorders, and the roles of nitrite/nitrate products (NOx) and low molecular weight-AGEs (LMW-AGEs) levels in this relationship. We carried out a case-control study (328 subjects) and determined genotypes by PCR. The rare-type TT of eNOS 894G>T was significantly overrepresented in patients without microvascular disorders as compared with control (OR=3.64; 95% C.I.=1.02–12.73; P=0.039). The prevalence of neuropathy was high among 894GG homozygotes (OR=0.5; 95% C.I.=0.29–0.86; P=0.012) who had high levels of triglycerides, elevated systolic BP, increased NOx, and LMW-AGEs. Decreased NOx levels were associated with 894TT genotype (beta=−0.65; P=0.043) in diabetic patients prone to microvascular complications. Multiple regression analysis indicated a negative correlation between eNOS 894G>T and diabetic neuropathy (P=0.025). The distribution of eNOS 4aa genotype was high (P=0.042) in patients with T1DM; however, it does not represent a risk factor for neuropathy. The overrepresentation of eNOS 894TT genotype in diabetic patients is associated with low risk for neuropathy. Decreased NOx and LMW-AGEs levels and lower lipid profile are the main features of patients carrying the eNOS 894T allele. These data suggest that the eNOS 894TT genotype may play a protective role by preventing microvascular disorders.     

The T-786C,G894T,and intron 4 VNTR (4a/b) polymorphisms of the endothelial nitric oxide synthase gene in prostate cancer cases

In previously conducted some studies it has been revealed that nitric oxide (NO) and nitric oxide synthase (NOS) system play a significant role in carcinogenesis. Nitric oxide (NO) is regulated by endothelial nitric oxide synthase (eNOS) enzyme which is one of the isoenzymes of NO synthase (NOS). In this study we have tried to come to a conclusion about whether eNOS gene T-786C, G894T and intron 4 VNTR (4a/b) polymorphisms might be considered as a risk factor causing prostate cancer (PCa) or not. A total of 200 subjects were included in this research. 84 patients with PCa (mean age 70.0 ± 6.4) and 116 healthy controls (mean age 69.9 ± 7.5) were recruited in this case-control study. Genomic DNA was extracted using the QIAamp DNA Blood Mini Kit (QIAGEN GmbH, Maryland, USA), according to the manufacturer’s guidelines. The T-786C, G894T and intron 4 VNTR (4a/b) polymorphisms were amplified using polymerase chain reation (PCR), detected by restriction fragment length polymorphism (RFLP). For T-786C polymorphism CC genotype [odds ratio (OR): 0.34, 95% confidence interval (CI): 0.15–0.78, P = 0.009)] and allele frequency (OR: 0.631, CI: 0.421–0.946, P = 0.026) is significant for control. In patients with PCa eNOS G894T polymorphism, both GT (OR: 0.069, CI: 0.027–0.174; P = 0.0001) and TT (OR: 0.040, CI: 0.013–0.123; P = 0.0001) genotype distribution, and also T allele frequency (OR: 0.237, CI: 0.155–0.362, P = 0.0001) were considered significant statistically. While genotype distribution for the other polymorphism eNOS, intron 4 VNTR (4a/b), is insignificant statistically, “a” allele frequency was found out to be significant (OR: 2.223, CI: 1.311–3.769, P = 0.003). In this study we indicated that genotype and allele frequencies of eNOS T-786C and G894T polymorphisms are statistically significant in patients with PCa. eNOS T-786C and G894T polymorphisms may be associated with PCa susceptibility in the Turkish population. In contrast, intron 4 VNTR (4a/b) polymorphism may not be related to PCa susceptibility in these patients.     

ACE、CYP11B2基因多态性与慢性心力衰竭患者醛固酮脱逸的关系

目的:研究CYP11B2-344C/T(醛固酮合成酶)及ACEI/D(血管紧张素转化酶)基因多态性与慢性心力衰竭(CHF)患者实施ACEI治疗后出现醛固酮脱逸表现的关系。方法:回顾分析2008年10月至2012年10月我科收治的252例CHF患者,全部患者应用ACEI治疗3月,醛固酮在基线以上为醛固酮脱逸,依据此标准将患者分为研究组(脱逸组,n=86)与对照组(非脱逸组,n=166),依据PCR(聚合酶链反应)及RFLP(片段长度限制多态性)等方法分别检测两组CYP11B2及ACE基因型,比较两组基因型频率的分布。结果:252例患者中,共86例出现醛固酮脱逸,发生率为34.1%。全部受试患者CYP11B2基因型及ACE基因型频率与Weinberg-Hardy平衡均相符(P均0.05)。研究组ACE I/D三种基因型的组间分布与对照组相较,无统计学差异(P0.05);CYP11B2基因TT型的频率与对照组相较,呈明显统计学差异(P0.05),等位基因C/T频率的组间分布同对照组相较,亦呈明显差异(P0.05)。研究组ACEI/D的基因多态性及CYP11B2-344C/T的多态性中,基因型联合组间分布与对照组相较,无统计学差异(P0.05)。结论:ACE基因多态性与CHF患者ACEI治疗后出现醛固酮脱逸无关,CYP11B2基因T等位基因及TT基因型多态性可能是CHF患者ACEI治疗后发生醛固酮脱逸的高危因素。醛固酮脱逸时,ACE、CYP11B2基因不具有协同效果。     

Endothelial nitric oxide synthase gene polymorphisms (G894T, 4b/a and T-786C) and preeclampsia: meta-analysis of 18 case-control studies

Studies investigating the association between endothelial nitric oxide synthase (eNOS) gene polymorphisms and preeclampsia reported contradictory or nonconclusive results. We performed a meta-analysis of 18 genetic association studies that examined the relationship between preeclampsia and the G894T, 4a/b and T-786C polymorphisms of the eNOS gene. Subgroup analysis by ethnicity and potential sources of heterogeneity and bias were explored. The MEDLINE, EMBASE, and Google Scholar databases were searched to access the relevant genetic association studies up to June 2011. For the allelic analysis of the G894T variant, all studies showed no significant association. For the genotypic analysis, the combined studies of the G allele showed negative significance (odds ratio [OR]=0.56; 95% confidence interval [CI]: 0.33-0.97), all the studies showed positively significance when the T allele was combined (OR=1.17; 95% CI: 1.01-1.36), and results were also positively significant in non-Asian populations (OR=1.20; 95% CI: 1.02-1.43). For the allelic analysis of the 4b/a variant, all studies showed no significant association, but results were negatively significant in non-Asian populations (OR=0.67; 95% CI: 0.46-0.98). For the genotype analysis, combined studies of the b allele showed negative significance (OR=0.55; 95% CI: 0.36-0.84). Moreover, non-Asian studies showed negatively significant results (OR=0.45; 95% CI: 0.28-0.72). For the analysis of the T-786C variant, none of the studies showed significant results. The synthesis of available evidence supports the fact that intron 4a allele, homozygosity for the 894T and intron 4a of eNOS are positively associated with preeclampsia. Large, multiethnic confirmatory, and well-designed studies are needed to determine the relation between preeclampsia and polymorphisms of the eNOS gene.     

Association of angiotensin-converting enzyme and endothelial Nitric Oxide synthase gene polymorphisms with vascular disease in ESRD patients in a Chinese population

Background The effect of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and endothelial Nitric Oxide synthase (eNOS) gene G894 → T on vascular disease in end-stage renal disease (ESRD) patients was rarely studied previously. We investigated such effect in a Chinese population. Methods A total of 153 ESRD patients with vascular disease (88 men and 65 women; mean age ± SD: 54.0 ± 13.2) were recruited. Polymerase chain reaction was used to classify the ACE genotypes as II, ID and DD and the eNOS genotypes as GG, GT, and TT. Analyses were performed in ESRD patients with vascular disease (n = 153) and the age-matched controls (n = 148). Results The frequencies of ACE DD and eNOS TT genotypes and ACE D and eNOS T alleles in ESRD patients with vascular disease were significantly higher than those in the controls (P < 0.05). There was a significant interaction between ACE I/D alleles and eNOS G894 → T polymorphism: adjusted odds ratio 2.128 (95%CI 1.022–4.434, P = 0.017). Conclusions These results indicated that the etiology of vascular disease in ESRD patients is associated with ACE and eNOS (G894 → T) gene polymorphisms. Our data also suggest that an interaction effect may exist between ACE (I/D) and eNOS (G894 → T) polymorphism in increasing the risk of vascular complications in ESRD patients     

eNOS基因（894G／T）多态性与HBV感染

为探讨HBV感染临床转归与eNOS基因多态性的关系,选择传染科门诊及住院部2002.2-2004.2诊治的无亲缘关系的重庆地区汉族居民2400人,采用聚合酶链反应(PCR)及限制性内切酶技术检测eNOS exon7位点894G/T多态性,应用SPSS软件χ2检验进行统计学处理:首先Hardy-Weinberg平衡检验Pa>0.01,表明拟合度优良,收集病例有良好的代表性;其次乙肝病毒携带与其余任何组比较(急乙肝与肝癌组因例数太少除外)等位基因频率与基因型频率Pb<0.05,乙肝病毒携带 慢乙肝组与肝硬化 重症肝炎组等位基因频率与基因型频率比较Pb<0.05。以非条件logistic回归校正年龄及性别因素进行分层分析,在隐性模式和共显性模式下,eNOS基因位点894G/T SNP与HBV感染后疾病的携带状态显著关联。与894G/T和T/T基因型相比,G/G基因型的个体发展为携带状态的易感性显著增高(隐性模式:OR=1.428 95%CI=1.050-1.942;共显性模式:OR=1.310 95%CI=1.025-1.676)。     

Interactions among Candidate Genes Selected by Meta-Analyses Resulting in Higher Risk of Ischemic Stroke in a Chinese Population

Ischemic stroke (IS) is a multifactorial disorder caused by both genetic and environmental factors. The combined effects of multiple susceptibility genes might result in a higher risk for IS than a single gene. Therefore, we investigated whether interactions among multiple susceptibility genes were associated with an increased risk of IS by evaluating gene polymorphisms identified in previous meta-analyses, including methylenetetrahydrofolate reductase (MTHFR) C677T, beta fibrinogen (FGB, β-FG) A455G and T148C, apolipoprotein E (APOE) ε2–4, angiotensin-converting enzyme (ACE) insertion/deletion (I/D), and endothelial nitric oxide synthase (eNOS) G894T. In order to examine these interactions, 712 patients with IS and 774 controls in a Chinese Han population were genotyped using the SNaPshot method, and multifactor dimensionality reduction analysis was used to detect potential interactions among the candidate genes. The results of this study found that ACE I/D and β-FG T148C were significant synergistic contributors to IS. In particular, the ACE DD + β-FG 148CC, ACE DD + β-FG 148CT, and ACE ID + β-FG 148CC genotype combinations resulted in higher risk of IS. After adjusting for potential confounding IS risk factors (age, gender, family history of IS, hypertension history and history of diabetes mellitus) using a logistic analysis, a significant correlation between the genotype combinations and IS patients persisted (overall stroke: adjusted odds ratio [OR] = 1.57, 95% confidence interval [CI]: 1.22–2.02, P < 0.001, large artery atherosclerosis subtype: adjusted OR = 1.50, 95% CI: 1.08–2.07, P = 0.016, small-artery occlusion subtype: adjusted OR = 2.04, 95% CI: 1.43–2.91, P < 0.001). The results of this study indicate that the ACE I/D and β-FG T148C combination may result in significantly higher risk of IS in this Chinese population.     

Association of the Glu298Asp polymorphism in the endothelial nitric oxide synthase gene with essential hypertension resistant to conventional therapy

Endothelial nitric oxide synthase (eNOS) produces nitric oxide (NO) which, after diffusing into vascular smooth muscle cells, activates guanylate cyclase leading to vasodilatation. A polymorphism (894G to T) in exon 7 of the eNOS gene causes the conversion of Glu to Asp in position 298. The recently described crystal structure of the heme domain of eNOS protein shows that Glu298 is fully solvent accessible and distant from regions integral to enzyme function. Searching for phenotypic expression of eNOS gene variants, we genotyped a group of patients with essential hypertension (H, n = 119) for the Glu298Asp polymorphism and compared them with age- and sex-matched healthy normals (N, n = 85). To specify phenotypic expression further, the hypertensive patients were subdivided into one group that responded well to regular antihypertensive therapy (CH, n = 45) and one group that was resistant to the therapy (RH, n = 74). Patients with BP higher than 140/90 mmHg when on adequate lifestyle modification and triple-combination therapy (including diuretics) were considered resistant. In RH and H groups, a significantly higher frequency of T alleles (P = 0.022 and P = 0.046, respectively) was found compared to normotonics (N). In well-controlled hypertonics, the same tendency was found, but did not reach statistical significance. The Glu298Asp polymorphism may contribute to the complex pathogenesis of essential hypertension and may be a factor in the resistance of these patients to conventional antihypertensive therapy. The presence of this allele may thus be predictive of the patients' therapeutic response.     

内皮型一氧化氮合酶基因多态性与高血压合并脑 梗塞的关系

目的:探讨内皮型一氧化氮合酶(eNOS)基因894G/T多态性与原发性高血压(EH)合并脑梗塞(CI)的关系。方法:应用聚合酶链反应限制性片段长度多态性方法检测湖北地区汉族74例健康者(NT组)、103例原发性高血压无合并症者(EH组)及70例原发性高血压合并脑梗塞者(EH-CI组)的eNOS基因型;生化技术测定其血脂、一氧化氮代谢物(NOM)水平。结果:EH组及EH-CI组患者的T等位基因频率分别为0.224和0.321,均显著高于NT组(P<0.05);且两者之间的T等位基因频率差异显著性(P<0.05);EH-CI组中,GT+TT基因型者的舒张压显著高于GG基因型者(P<0.05),而NOM显著低于GG基因型者。结论:eNOS基因894位G/T多态性可能与汉族高血压病患者伴脑梗塞有关,该位点多态性可能使T等位基因携带者NOM减少,进而参与EH-CI发病。     

ENOS-G894T polymorphism is a risk factor for essential hypertension in China

Vascular endothelial cells produce nitric oxide (NO), which contributes to the regulation of blood pressure and regional blood flow. Polymorphisms of the endothelial nitric oxide synthase (eNOS) gene are associated with coronary artery disease; however, associations between polymorphism (G894T) of the eNOS gene and essential hypertension remain unclear. This study was designed to investigate the association between a eNOS-G894T polymorphism and essential hypertension (EH). A total of 190 Chinese EH patients (EH group) and 94 healthy participants (control group) were included in the study. eNOS-G894T was determined using multi-polymerase chain reaction and polymorphisms in eNOS-G894T were genotyped using gene chip technology. Patients carrying eNOS GT + TT genotypes had a higher risk of EH than those carrying the GG genotype (OR = 2.82, 95% CI: 1.05-7.60, P = 0.033). The EH group showed a significantly higher frequency of the T-allele compared with controls (OR = 3.48, 95% CI: 1.34-9.07; P = 0.007). eNOS-894T was found to be significantly associated with EH in the dominant genetic model. Thus, the study demonstrated a significant and independent association between a eNOS-G894T polymorphism and EH in the Chinese patients. The study also showed that eNOS-G894T polymorphism is a risk factor for EH in Chinese patients.     

Influence of eNOS haplotypes on the plasma nitric oxide products concentrations in hypertensive and type 2 diabetes mellitus patients.

Endothelial nitric oxide synthase (eNOS) haplotypes are associated with hypertension (HT) in patients with or without type 2 diabetes mellitus (T2DM). We evaluated the association of eNOS genotypes/haplotypes with the plasma concentrations of nitrite/nitrate (NO(x)), which are products of nitric oxide in HT, T2DM, and T2DM+HT patients. We studied eNOS polymorphisms in the promoter region (T-786C), in exon 7 (Glu298Asp), and in intron 4 (b/a) in 98 controls, 68 patients with HT, 66 patients with T2DM, and 86 patients with T2DM+HT. NO(x) concentrations were assessed using a chemiluminescence assay. No differences were found in genotype/allele distribution among groups. Genotypes were not associated with NO(x) concentrations. The "C-Glu-b" haplotype was more common in controls than in HT/T2DM+HT groups (21% versus 9/5%, respectively, P<0.006). This haplotype was more common in HT and T2DM+HT groups among subjects with high (82+/-38 and 90+/-33 microM, respectively) than with low (35+/-7 and 34+/-7 microM, respectively) NO(x) concentrations. Conversely, the "C-Asp-b" haplotype was more common in HT/T2DM+HT groups than healthy (21/21% versus 10%, respectively, P<0.006). The haplotype associated with lower risk of developing hypertension is also associated with higher NO(x) levels among hypertensives. Conversely, the haplotype increasing the risk of developing hypertension is associated with lower NO(x) levels in hypertensives.     

Interaction of eNOS polymorphism with MTHFR variants increase the risk of diabetic nephropathy and its progression in type 2 diabetes mellitus patients

The present study has investigated the role of endothelial nitric oxide (eNOS) G894T polymorphism and its interaction with methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C variants on the predisposition to diabetic nephropathy and its progression. Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method the eNOS G894T and MTHFR polymorphisms were detected in 72 microalbuminuric, 68 macroalbuminuric, and 72 normoalbuinuric type 2 diabetes mellitus (T2DM) patients from Western Iran. The presence of GT and GT + TT genotypes of eNOS were associated with insignificantly 1.86- and 1.68-fold increased risk of macroalbuminuria, respectively and 1.21- and 1.13-fold increased risk of microalbuminuria, respectively. However, the concomitant presence of eNOST and MTHFR 1298C alleles were significantly increased the risk of macroalbuminuria (6.6-fold, P < 0.001) and progression from micro- to macro-albuminuria (3.85 times, P = 0.011). Also, the presence of both alleles of eNOST and MTHFR 677T were significantly associated with increased risk of macroalbuminuria (4.8-fold, P = 0.005). The presence of GT + TT genotypes of eNOS was significantly associated with increased risk of coronary artery disease in micro- and macro-albuminuric patients compared to normoalbuminuric patients. The concomitant presence of three mutant alleles significantly increased the risk of macroalbuminuria and progression from micro- to macro-albuminuria 38.5- and 10.5-fold, respectively. Our study indicated that eNOS T allele interacts with MTHFR variants, especially MTHFR A1298C to increase the risk of macroalbuminuria and progression from micro-to macro-albuminuria. Also, Interaction between three alleles of eNOST, MTHFR 677T, and 1298C highly increased the risk of macroalbuminuria and progression of diabetic nephropathy in T2DM patients.     

Cotyledon and binucleate cell nitric oxide synthase expression in an ovine model of fetal growth restriction.

Heat exposure early in ovine pregnancy results in placental insufficiency and intrauterine growth restriction (PI-IUGR). We hypothesized that heat exposure in this model disrupts placental structure and reduces placental endothelial nitric oxide synthase (eNOS) protein expression. We measured eNOS protein content and performed immunohistochemistry for eNOS in placentas from thermoneutral (TN) and hyperthermic (HT) animals killed at midgestation (90 days). Placental histomorphometry was compared between groups. Compared with the TN controls, the HT group showed reduced delivery weights (457 +/- 49 vs. 631 +/- 21 g; P < 0.05) and a trend for reduced placentome weights (288 +/- 61 vs. 554 +/- 122 g; P = 0.09). Cotyledon eNOS protein content was reduced by 50% in the HT group (P < 0.03). eNOS localized similarly to the vascular endothelium and binucleated cells (BNCs) within the trophoblast of both experimental groups. HT cotyledons showed a reduction in the ratio of fetal to maternal stromal tissue (1.36 +/- 0.36 vs. 3.59 +/- 1.2; P< or = 0.03). We conclude that eNOS protein expression is reduced in this model of PI-IUGR and that eNOS localizes to both vascular endothelium and the BNC. We speculate that disruption of normal vascular development and BNC eNOS production and function leads to abnormal placental vascular tone and blood flow in this model of PI-IUGR.     

Association of a polymorphism of the angiotensin I-converting enzyme gene with essential hypertension.

Angiotensin I-converting enzyme (ACE) is responsible for production of angiotensin II and breakdown of kinins, leading to increased blood pressure (BP). Furthermore, ACE inhibitors are effective antihypertensive agents. A 287 bp insertion/deletion polymorphism in intron 16 of the ACE gene (ACE) was examined by PCR in a cross-sectional study of 80 hypertensive (HT) and 93 normotensive (NT) subjects whose parents had a similar BP status at age greater than or equal to 50. The frequency of the insertion allele was 0.56 in HTs and 0.41 in NTs, and the difference between observed alleles in all subjects in each group was significant (chi 2 = 7.6, P less than 0.01). The data thus provide evidence in favour of an association of HT with a polymorphism at the ACE locus (17q23), so implicating this locus, and possibly a genetic variant of ACE itself, in human essential hypertension.     

脂联素基因单核苷酸多态性与Ⅱ型糖尿病合并肥胖及胰岛素抵抗相关联

脂联素是近年新发现的脂肪组织特异性的细胞因子,其mRNA是脂肪组织中含量最丰富的基因转录产物,该因子可通过多种途径影响个体对胰岛素的敏感性。脂联素基因多态性与肥胖、胰岛素抵抗和2型糖尿病密切相关,而与冠心病相关性研究的报道较少。本研究以中国汉族人群1,098例为对象,其中304例冠心病(CHD)患者,389例糖尿病患者(T2DM),及405例性别年龄相匹配的正常对照,采用PCR-RFLP技术对脂联素基因-4522C/T进行基因分型,并分别对血脂水平、胰岛素抵抗、体重指数等临床数据进行分析比较。研究结果显示,脂联素基因-4522C/T各基因型及等位基因在CHD组与对照组、T2DM组与对照组中的分布差异无显著性;经分组分析发现,T2DM合并肥胖患者BMI≥25kg/m2TT基因型及T等位基因明显多于对照组,差异有显著性,P=0.014和P=0.034;TT基因型T2DM患者胰岛素抵抗指数(HOMA-IR)显著高于携带有C等位基因的T2DM患者,P=0.0069。本研究提示脂联素基因-4522C/T与中国汉族人群T2DM合并肥胖的发生及T2DM患者胰岛素抵抗相关,是引发糖尿病患者肥胖和胰岛素抵抗的重要候选基因,而与冠心病的发生无关联。     

Endothelial nitric oxide synthase g894t (rs1799983) gene polymorphism in polish athletes

The NOS3 gene has been associated with athletic endurance performance and elite power athletic status. With respect to NOS3 G894T and its relation to athletic performance or status, results across various studies have not been consistent. Therefore, the lack of consistency among previous studies prompted us to design a case-control study in a Polish Caucasian population to examine the relationship between the NOS3 G894T polymorphism and athletes' status, i.e. type and intensity of exercise performed (poweroriented, “mixed” power/endurance activity, endurance-oriented) and the possible association between the G894T variant and athletic performance. The case-control study was performed in a group of 360 Polish athletes (cases) of the highest nationally competitive standard (male n=156 and female n=67) and 191 unrelated, sedentary control subjects. The G894T genotype and allele distributions differed significantly between power-oriented (P=0.009, P=0.003), “mixed” (P=0.021, P=0.009), endurance (P=0.043, P=0.014) athletes when compared to control subjects (P values for genotypes and alleles, respectively). There were no significant differences between elite and sub-elite athletes in any group. The over-representation of the GG genotype and G allele in all athletes suggests that the G894 allele may favour all types of sports, however, the strongest predisposition was seen among power-oriented athletes.     

Deletion polymorphism of the angiotensin I-converting enzyme gene in elderly patients with coronary heart disease

Controversy exists as to whether the deletion/deletion (DD) genotype of angiotensin l-converting enzyme (ACE) gene polymorphism is associated with coronary heart disease (CHD). There are only a few studies dealing with this issue in the elderly, also with controversial results. The aim of this study was the assessment of correlation between genetic markers and the risk of CHD in the elderly. The results indicated DD genotype importance for CHD in the elderly as proven by discriminant analysis (chi2 = 25.77; df = 16; p = 0.0620). However, the use of univariate method demonstrated no correlation between DD genotype of ACE gene polymorphism and coronary artery disease. D allele of ACE gene was associated with higher activities of ACE plasma. A weak, but increased risk of MI is associated with high frequency of DD genotype in the elderly. Strong correlation between ACE polymorphism and ACE plasma activities was demonstrated.