Association of angiotensinogen gene M235T polymorphism with the risk of IgA nephropathy: a meta-analysis

The association between angiotensinogen (AGT) M235T gene polymorphism and IgA nephropathy (IgAN) risk remains elusive. Our aim was to evaluate the association between AGT M235T gene polymorphism and IgAN susceptibility by performing a meta-analysis. Eligible studies were searched according to predefined criteria using electronic databases. Eight studies were identified for the analysis of the association between AGT M235T gene polymorphism and IgAN risk. M allele/MM genotype were not associated with IgAN risk in overall populations, Caucasians and Asians (overall populations: p?=?0.448 and 0.861, Caucasians: p?=?0.618 and 0.886, Asians: p?=?0.566 and 0.652). TT/MT genotype were not associated with IgAN risk in overall populations, Caucasians and Asians (overall populations: p?=?0.703 and 0.454, Caucasians: p?=?0.975 and 0.946, Asians: p?=?0.697 and 0.353). No evidence of publication bias was observed. In conclusion, AGT M235T gene polymorphism may not be correlated with IgAN susceptibility in overall populations, Caucasians and Asians. However, more studies should be performed in the future.     

Association of Megsin 2093C/T, 2180C/T and C25663G gene polymorphism with the risk of IgA nephropathy

The association between megsin 2093C/T, 2180C/T and C25663G gene polymorphisms and IgA nephropathy (IgAN) risk remains unclear. We aimed to evaluate the association between megsin 2093C/T, 2180C/T and C25663G gene polymorphisms and IgAN risk by performing a meta-analysis. Eligible studies were searched according to predefined criteria by using electronic databases. Six articles were identified for the analysis of the association between megsin 2093C/T, 2180C/T and C25663G gene polymorphisms and IgAN risk. 2093C/T C allele was associated with IgAN risk in overall populations and Asians (overall populations: p?=?0.014, Asians: p?=?0.037). 2093C/T CC/TT genotype was not associated with IgAN risk in overall populations, Caucasians and Asians. 2180C/T C allele was correlated with IgAN risk in Caucasians (p?=?0.024). 2180C/T CC/TT genotype was not associated with IgAN risk in overall populations, Caucasians and Asians. C25663G gene polymorphism was not associated with IgAN onset in Asians. In conclusion, megsin 2093C/T C allele may be genetic marker for IgAN susceptibility in overall populations and Asians. 2180C/T C allele may be risk factor for IgAN onset in Caucasians. However, more studies should be performed in the future.     

Lack of association of angiotensin II type 1 receptor A1166C gene polymorphism with the risk of end-stage renal disease

Abstract

The association between angiotensin II type 1 receptor (AT1R) A 1166C (rs5186) gene polymorphism and end-stage renal disease (ESRD) risk remains controversial. We aimed to assess the association between AT1R A1166C gene polymorphism and ESRD susceptibility by performing a meta-analysis. Eligible studies were searched according to a predefined criterion using electronic databases. Eight articles were identified for the analysis of the association between AT1R A1166C gene polymorphism and ESRD risk. A allele and AA genotype were not associated with ESRD risk in overall populations, Caucasians and Asians (overall populations: p?=?0.834 and 0.832, Caucasians: p?=?0.853 and 0.884, Asians: p?=?0.243 and 0.982). CC and AC genotype were not associated with ESRD risk in overall populations, Caucasians and Asians (overall populations: p?=?0.304 and 0.712, Caucasians: p?=?0.510 and 0.987, Asians: p?=?0.319 and 0.225). In conclusion, AT1R A1166C gene polymorphism may not be correlated with ESRD risk in overall populations, Caucasians and Asians. However, more studies should be performed in the future.     

Meta-analysis of the relationship between ACE I/D gene polymorphism and end-stage renal disease in patients with diabetic nephropathy

Aims: Diabetic nephropathy (DN) is the major cause for end‐stage renal disease (ESRD) and the pathogenesis for DN developing into ESRD is not clear at present. Results from published studies on the relationship between angiotensin‐converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and ESRD risk in DN patients are still conflicting. This meta‐analysis was performed to evaluate the association between ACE I/D gene polymorphism and ESRD risk in DN patients. Methods: Association studies were identified from the databases of PubMed, Embase and Cochrane Library on 1 October 2011, and eligible investigations were identified and synthesized using the meta‐analysis method. Results were expressed using odds ratios (OR) for dichotomous data and 95% confidence intervals (CI) were also calculated. Results: Twelve studies reporting the relation between ACE I/D gene polymorphism and ESRD risk in DN patients were identified. In overall populations, there was a notable association between D allele or DD genotype and ESRD susceptibility (D: OR = 1.32, 95% CI: 1.11–1.56, P = 0.002; DD: OR = 1.67, 95% CI: 1.25–2.21, P = 0.0004). In the sub‐group analysis according to ethnicity, D allele or DD genotype was associated with ESRD risk in Asians. In Caucasians, the association of DD genotype with ESRD risk was observed, but the D allele was not. Furthermore, ACE I/D gene polymorphism was associated with ESRD risk in patients with DN due to diabetes mellitus type 2, but the association was not found for patients with DN due to diabetes mellitus type‐1. Conclusions: Our results indicate that D allele or DD homozygous is associated with the ESRD susceptibility in DN patients. However, more investigations are required to further this association.     

Methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism and diabetic nephropathy susceptibility in patients with type 2 diabetes mellitus

Abstract

Methylenetetrahydrofolate reductase (MTHFR) is a crucial enzyme that regulates nucleotide synthesis and DNA methylation. The MTHFR C677T gene polymorphism (rs1801133), a C?→?T transition at nucleotide 677 in exon 4, is a common gene variant of MTHFR and has been implicated in diabetic nephropathy, albeit with inconsistent results. Here, we performed a meta-analysis to assess the common effect size of this polymorphism on DN susceptibility. Case–control studies on the association of the MTHFR C677T gene polymorphism with DN risk were retrieved from databases up to August 1, 2013, and eligible studies were recruited into the meta-analysis and further analyzed. Of 132 studies, 33 were identified as suitable for this analysis. The results showed that T allele and TT genotype were distinctly associated with DN susceptibility in the overall population and Asians, and might be a risk factor in Caucasians and Africans (T allele: Overall population: p?<?0.00001, Asians: p?=?0.0002, Caucasians: p?=?0.02, Africans: p?<?0.00001; TT genotype: Overall population: p?<?0.00001, Asians: p?=?0.0003, Caucasians: p?=?0.008, Africans: p?=?0.0003). Furthermore, the analysis suggested that the CC genotype might play a protective role against DN onset in patients with type 2 diabetes for the overall population, Asians, Caucasian and Africans. However, due to the limited sample size in the African population, these results should be interpreted with care. In conclusion, the MTHFR C677T T allele or TT genotype might be a significant genetic molecular marker to determine the risk of DN in patients with type 2 diabetes and help to develop suitable disease prevention and management strategies.     

Glu298Asp endothelial nitric oxide synthase polymorphism is a risk factor for erectile dysfunction in the Mexican Mestizo population

Penile erection depends on the balanced action between antagonist vasoactive molecules such as nitric oxide (NO) and angiotensin. Endothelial nitric oxide synthase (eNOS) and angiotensin-converting enzyme (ACE) polymorphisms have been associated with endothelial dysfunction, which is described as a cause of erectile dysfunction (ED). Endothelial NOS and ACE are both regulators of vascular and corporal smooth muscle tone, which are connected by interaction between the NO-cyclic guanosine monophosphate pathway and the renin-angiotensin system. We analyzed the frequencies of 894 G/T (Glu298Asp) eNOS and ACE I/D polymorphisms in Mexican patients with ED (n=53) and in an age-matched control group (n=62). The populations analyzed were in Hardy Weinberg equilibrium. We found significant differences in allelic (chi2=4.42; P=.03) and genotypic frequencies (chi2=3.96; P=.04) between patients and controls for the 894 G/T eNOS polymorphism. Presence of the 894T allele in carriers increased the risk of ED (odds ratio [TT + GT versus GG] = 2.37; 95% confidence interval, 1.08 to 5.21; P=.02). Multiple logistic regression analysis showed that the Glu298Asp polymorphism was an independent factor for ED, as was diabetes mellitus, hypertension, cardiac disease, and cigarette smoking. No association was found between ACE I/D polymorphism and ED in the population studied. Therefore, our results suggest that Glu298Asp eNOS polymorphism plays a role as a genetic susceptibility factor for ED.     

Association of transforming growth factor-β1 polymorphisms with the risk of chronic kidney diseases

Abstract

The association of transforming growth factor-β1 (TGF-β1) polymorphisms with the risk of chronic kidney diseases (CKD) remains elusive. We aimed to perform a meta-analysis to evaluate the relationship between TGF-β1 polymorphisms and the susceptibility to CKD. Association studies were searched according to a defined criteria using electronic databases. The strength of association between TGF-β1 polymorphisms and CKD risk was evaluated by odds ratio (OR) with the corresponding 95% confidence interval (CI). Nine case–control studies were identified. T allele at the +869 T/C polymorphism was associated with a lower risk of CKD in Asians (p?=?0.003). TT genotype at the +869 T/C polymorphism was associated with a lower risk of CKD in overall populations and Asians (p?=?0.007 and <10^?4, respectively). CC genotype at the +869 T/C polymorphism was associated with the risk of CKD in Asians (p?=?0.002). T allele at the ?509 T/C polymorphism was associated with the risk of CKD in overall populations and Asians (p?=?0.044 and 0.050, respectively). TT genotype at the ?509 T/C polymorphism was associated with CKD risk in overall populations, Caucasians and Asians (p?<?10^?4, <10^?4, and <10^?4, respectively). No evidence of significant publication bias was noted. In conclusion, T allele at the +869 T/C polymorphism may be a protective factor against CKD risk in Asians. TT genotype at the +869 T/C polymorphism may be an indicator of lower risk of CKD in overall populations and Asians. CC genotype at the +869 T/C polymorphism may predict the susceptibility to CKD in Asians. T allele at the ?509 T/C polymorphism may be an indicator of CKD risk in overall populations and Asians. TT genotype at the ?509 T/C polymorphism was a risk factor for CKD onset in overall populations, Caucasians and Asians.     

Insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme gene in steroid-resistant nephrotic syndrome for children: a genetic association study and meta-analysis

An assessment of the association of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with steroid-resistant nephrotic syndrome (SRNS) risk in children is still controversial. A meta-analysis was performed to evaluate the relation between ACE gene polymorphisms and SRNS susceptibility. The relevant studies were screened from electronic database and eligible investigations were synthesized using meta-analysis methods. Seven investigations were identified for the analysis of association between ACE I/D gene polymorphism and SRNS risk in children, including five in Asians, one in Caucasians, and one in Africans. There was not a markedly positive association between D allele or DD genotype and SRNS susceptibility in Asians (OR = 1.60, p = 0.26; OR = 1.90, p = 0.38) and for Caucasian population (OR = 0.92, p = 0.86; OR = 0.27, p = 0.22). However, an association of D allele with SRNS susceptibility was observed (OR = 4.67, p = 0.003) in Africans, but not for DD genotype (OR = 6.00, p = 0.05). Interestingly, II genotype seemed to play a positive role against SRNS onset for Asians and African children (OR = 0.51, p = 0.02; OR = 0.07, p = 0.02), but not for Caucasians (OR = 0.33, p = 0.30). In conclusion, our results indicate that D allele or DD homozygous might not be a significant genetic molecular marker for the development of SRNS in Asians and Caucasian children. However, D allele seemed be associated with SRNS risk for Africans but DD genotype did not.     

Insertion/Deletion (I/D) Polymorphism of Angiotensin-Converting Enzyme Gene in Steroid-Resistant Nephrotic Syndrome for Children: A Genetic Association Study and Meta-analysis

Abstract

An assessment of the association of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with steroid-resistant nephrotic syndrome (SRNS) risk in children is still controversial. A meta-analysis was performed to evaluate the relation between ACE gene polymorphisms and SRNS susceptibility. The relevant studies were screened from electronic database and eligible investigations were synthesized using meta-analysis methods. Seven investigations were identified for the analysis of association between ACE I/D gene polymorphism and SRNS risk in children, including five in Asians, one in Caucasians, and one in Africans. There was not a markedly positive association between D allele or DD genotype and SRNS susceptibility in Asians (OR = 1.60, p = 0.26; OR = 1.90, p = 0.38) and for Caucasian population (OR = 0.92, p = 0.86; OR = 0.27, p = 0.22). However, an association of D allele with SRNS susceptibility was observed (OR = 4.67, p = 0.003) in Africans, but not for DD genotype (OR = 6.00, p = 0.05). Interestingly, II genotype seemed to play a positive role against SRNS onset for Asians and African children (OR = 0.51, p = 0.02; OR = 0.07, p = 0.02), but not for Caucasians (OR = 0.33, p = 0.30). In conclusion, our results indicate that D allele or DD homozygous might not be a significant genetic molecular marker for the development of SRNS in Asians and Caucasian children. However, D allele seemed be associated with SRNS risk for Africans but DD genotype did not.     

Association of angiotensin I-converting enzyme gene insertion/deletion polymorphism and IgA nephropathy: a meta-analysis

BACKGROUND/AIMS: The angiotensin I-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism has been extensively examined for the association with immunoglobulin A (IgA) nephropathy (IgAN), however, conflicting results have occurred. We performed a meta-analysis to evaluate the association of ACE I/D polymorphism with IgAN in different ethnic groups. METHODS: 11 studies testing the association between ACE I/D polymorphism and IgAN susceptibility, and 9 studies testing the association of ACE I/D with IgAN progression were used in this analysis. The overall odds ratio (OR) was estimated by a fixed or random effect model. RESULTS: The overall OR for the risk of susceptibility and progression of IgAN in Asians for the DD genotype is 2.37 (95% CI 1.04-5.41) and 1.75 (95% CI 1.24-2.56). The overall OR for the D allele in Asians also showed a similar magnitude, though without statistical significance (p = 0.09, p = 0.13, respectively). In Caucasians, both the DD genotype and D allele were associated with IgAN progression (OR 1.90, 1.61, respectively), but not IgAN susceptibility (p = 0.30, p = 0.41, respectively). CONCLUSION: Our findings support the notion that ACE I/D polymorphism is associated with IgAN. Meanwhile, the role of ACE I/D polymorphism in Asians is different from that of Caucasians.     

4 G/4 G polymorphism of plasminogen activator inhibitor-1 gene increases the risk of diabetic nephropathy

Diabetic nephropathy (DN) has become the most common pathogenesis of end-stage renal disease. Plasminogen activator inhibitor-1 (PAI-1) plays an important role in the pathogenesis of DN. A meta-analysis was conducted to investigate the association between 4?G/5?G variants in the PAI-1 gene and DN susceptibility. Databases including Pubmed, EMBASE, ISI, etc., were searched to find relevant studies. Odds ratios (ORs) with 95% con?dence intervals (CIs) were used to evaluate the strength of associations. Ten studies involving 1366 cases and 1888 controls were included. Significant association between 4?G/4?G variant and DN risk was observed (OR 1.26, 95% CI 1.08–1.48, p?=?0.004) in overall populations by the recessive model. 4?G allele was also associated with the risk of DN than the 5?G allele (OR 1.15, 95% CI 1.04–1.27, p?=?0.008). In the subgroup analysis performed by the ethnicity, 4?G/4?G polymorphism was significantly associated with DN risk than 4?G/5?G?+?5?G/5?G in East Asians (OR 1.42, 95% CI 1.03–1.96; p?=?0.03), but not in Caucasians. In the strati?ed analysis by types of DM, the results showed significant association between 4?G/4?G variant and DN in Type-2 DM (OR 1.42, 95% CI 1.03–1.96, p?=?0.03). In conclusion, 4?G/4?G phenotype of PAI-1 gene may be associated with DN risk. Additional larger studies should be conducted in future analyses.     

Common variants of the endothelial nitric oxide synthase gene and the risk of coronary heart disease among U.S. diabetic men

Endothelial nitric oxide synthase (eNOS) gene represents a promising candidate gene for coronary heart disease (CHD) because of its impact on eNOS activity. We systematically examined the associations of eight variants of the eNOS gene (two potentially functional variants [-786T>C and Glu298Asp] and six tagging single nucleotide polymorphisms) with CHD risk in a large cohort of diabetic patients. Among 861 diabetic men (>97% Caucasian) from the Health Professionals Follow-Up Study, 220 developed CHD, and 641 men without cardiovascular disease were used as control subjects. Genotype distributions of -786T>C and Glu298Asp polymorphisms were not significantly different between case and control subjects. CHD risk was significantly higher among men with the variant allele at the rs1541861 locus (intron 8 A/C) than men without it (adjusted odds ratio 1.5 [95% confidence interval 1.1-2.1]). Moreover, among control subjects, plasma soluble vascular cell adhesion molecule concentrations were significantly higher among carriers of this allele (P 0.019) and carriers of the variant allele of the -786T>C (P 0.010), or the Glu298Asp polymorphism (P 0.002), compared with noncarriers. In conclusion, our data suggested that -786T>C, Glu298Asp, and an intron 8 polymorphism of the eNOS gene are potentially involved in the atherogenic pathway among U.S. diabetic men.     

内皮型一氧化氮合成酶基因Glu298Asp多态性与糖尿病肾脏病的关系

目的探讨内皮型一氧化氮合成酶（eNOS）基因Glu298Asp多态性与糖尿病肾脏病（DIcD）的关系。方法采用聚合酶链反应（PCR）后限制性内切酶消化技术，对在我院就诊的326例中国汉族2型糖尿病（T2DM）患者和215名健康体检者进行Glu298Asp基因型分析。根据尿白蛋白排泄率（UAER）水平将T2DM患者分为3组：UAER正常组（DM组）102例，微量白蛋白尿组（MAU组）81例，临床肾病组（DKD组）143例。选择同时期本院健康体检者215名为对照组。用多因素Logistic回归分析法判定DKD的独立危险因素。结果DKD组与对照组Glu298Asp基因型频率分布存在显著性差异（GG72．72％、GT26．57％、TT0．70％比GG83．41％、GT16．10％、TT0．49％，P=0．019），而DM组和MAU组则与对照组无差异（P〉0．05）。Logistic回归分析显示，年龄、平均动脉压、GT基因型是DKD发生的独立危险因素。结论eNOS Glu298Asp基因与中国汉族T2DM患者DKD具有相关性。     

Diabetes mellitus and late‐onset hypogonadism: the role of Glu298Asp endothelial nitric oxide synthase polymorphism

Nitric oxide has been associated with insulin resistance and type 2 diabetes mellitus (DM). An association has been suggested between a single nucleotide polymorphism (Glu298Asp variant) of the endothelial nitric oxide synthase (eNOS) gene and increased risk of DM. However, the role of this polymorphism in favouring DM has not been investigated in hypogonadism, in which low testosterone and obesity are believed to play the major role. We aimed to evaluate whether eNOS gene single nucleotide polymorphism (Glu298Asp variant) might give a relevant contribution also to the onset of hypogonadism‐associated DM. 110 men affected by late‐onset hypogonadism were retrospectively reviewed. Patients were clinically and biochemically evaluated. Detection of eNOS Glu298Asp polymorphism was performed. After splitting the sample according to the three genetic variants (i.e. eNOS_GG, eNOS_GT, eNOS_TT), no difference was evident in age, body mass index (BMI) and total testosterone. Conversely, DM prevalence, glycaemia and glycated haemoglobin were significantly higher in eNOS_TT than in eNOS_GT and eNOS_GG. Logistic regression analysis showed that, after adjustment for age, BMI and total testosterone, eNOS_TT was positively and significantly associated with DM. Our study suggests that Glu298Asp single nucleotide polymorphism of the eNOS gene may be an independent risk factor for hypogonadism‐associated type 2 DM.     

Endothelial nitric oxide synthase gene polymorphisms in patients with nontraumatic femoral head osteonecrosis.

As endothelial nitric oxide synthase (eNOS) has beneficial effects on skeletal, vascular, and thrombotic systems, the association between nontraumatic femoral head osteonecrosis (FHON) and eNOS gene polymorphisms was investigated in Korean patients with FHON. Genomic DNA from 103 patients with nontraumatic FHON (idiopathic in 50, steroid-induced in 29, and alcohol abuse in 24) and 103 control subjects matched for gender and age (3-year range) was analyzed for the 27-bp repeat polymorphism in intron 4 and Glu298Asp polymorphism in exon 7. The frequencies of alleles and genotypes were compared between patients and control subjects. The frequency of 4a allele was significantly higher in total patients than control subjects [6.8% vs. 2.4%, p = 0.0345, odds ratio (OR) 2.931]. In subgroup analysis, the 4a allele significantly increased in patients with idiopathic FHON versus control subjects (9.0% vs. 2.4%, p = 0.0297, OR 3.976). The frequency of the 4a/b genotype in total patients (13.6% vs. 4.9%, p = 0.0302, OR 3.083) as well as patients with idiopathic FHON (18.0% vs. 4.9%, p = 0.0246, OR 4.302) was higher than control subjects. The distribution of Glu298Asp polymorphisms was not significantly different between patients and control subjects. Microstellate polymorphism in intron 4 of eNOS polymorphism was significantly associated with idiopathic FHON in Korean patients. Because 4a allele is associated with lower synthesis of eNOS, these results suggest that carrier state of 4a allele in intron 4 might be a genetic risk factor of FHON and could provide insight into the protective role of nitric oxide in the pathogenesis of FHON.     

Association of endothelial nitric oxide synthase gene polymorphisms with end-stage renal disease: a systematic review and meta-analysis

Background and objective: Endothelial nitric oxide synthase (eNOS) is one of the potent regulators of intra renal hemodynamics. Polymorphisms of eNOS gene may be involved in the progression of renal disease, and may be the causative factors that contribute to the deterioration of renal functions. During the past decades, several studies investigated the association of eNOS polymorphisms with the risk of end-stage renal disease (ESRD), but the results remain unclear and the mechanisms are not defined. Our study was designed to examine the role of different eNOS genetic polymorphisms in the progression of ESRD. Materials and methods: Relevant studies were identified through PubMed, Embase, Medline and CNKI (China National Knowledge Infrastructure) database published between January 2000 and November 2013. The association between eNOS polymorphisms and ESRD susceptibility was assessed by pooled odds ratios (ORs) and 95% confidence intervals (95% CI) in fixed or random effects models. Results: Sixteen articles were identified for the analysis of association between eNOS gene polymorphisms and ESRD risk. A total of 2729 patients and 2190 controls for 4b/a, 851 patients and 1171 controls for G894T, and 513 patients and 487 controls for T786C were included in our analysis. Overall, 4a allele of 4b/a polymorphism produced a significant association in the global population (OR?=?1.47, 95% CI?=?1.05–2.06, p?=?0.03) in a random-effect model; T allele of G894T was also significantly associated with ESRD susceptibility in overall populations (OR?=?2.12, 95% CI?=?1.44–3.12, p?=?0.0001). Furthermore, 4a and T carriers were significantly associated with ESRD risk as well. No association was found between T786C polymorphism and ESRD. Conclusion: The evidence accumulated suggested that 4b/a and G894T polymorphisms in the eNOS gene were associated with ESRD susceptibility, indicating that 4a and T allele carriers might become significant genetic molecular markers for the onset of ESRD in overall populations. However, more studies should be performed in the further studies.     

Association between MCP-1 2518 A&gt;G gene polymorphism and chronic kidney disease

Monocyte chemoattractant protein-1 (MCP-1) is involved in the pathogenesis of chronic kidney diseases (CKD). MCP-1 2518 A>G gene polymorphism is associated with MCP-1 status. We performed a meta-analysis to assess the association between MCP-1 2518 A>G gene polymorphism and CKD risk. The eligible studies regarding the relationship between MCP-1 2518 A>G gene polymorphism and CKD risk were searched through electronic databases. The pooled odds ratios (ORs) and its 95% confidence intervals (CIs) were calculated by using a fixed-effects model, or in the presence of heterogeneity, a random-effects model. A total of 2415 cases and 2011 controls were recruited in our investigation. A allele/GG genotype was not associated with CKD risk in overall populations, Asians, Caucasians, and Africans. AA/AG genotype was not associated with the risk of CKD in overall populations, Asians, Caucasians, and Africans. AA genotype was associated with a lower risk of CKD in Caucasians (OR 0.816, 95% CI 0.703–0.947). AG genotype was associated with a higher risk of CKD in Caucasians (OR 1.230, 95% CI 1.042–1.452). There was no marked publication bias. In conclusion, AA genotype may be a protective factor against CKD susceptibility in Caucasians. AG genotype may be a risk factor for CKD risk in Caucasians. However, more studies are needed in the future.     

内皮型一氧化氮合酶Glu298Asp基因多态性与老年原发性高血压微量白蛋白尿的关系

目的研究内皮型一氧化氮合酶（eNOS）Glu298Asp基因多态性与老年原发性高血压（EH）微量白蛋白尿（MAU）的关系。方法从到医院就诊的老年EH患者中筛选出202例无显性蛋白尿的患者,行24h MAU测定,并应用基因芯片技术检测eNOS Glu298Asp基因多态性,按照24hMAU定量分为MAU组和非MAU组（NAU组）,比较两组基因型和等位基因分布差异。结果两组等位基因和基因型的分布不同,MAU组等位基因T及含等位基因T的基因型（GT＋TT）分布频率明显升高（χ^2=6.62,P〈0.01;χ^2=7.29,P〈0.01）;T等位基因变异使老年EH患者MAU的相对危险度显著增高（OR=2.361,95%CI=1.256～4.437）。结论 T等位基因是老年EH患者MAU的易感基因,携带T等位基因导致老年EH患者出现MAU的风险显著增高。     

Methylenetetrahydrofolate reductase C677T polymorphism and the risk of male infertility: a meta-analysis

Several molecular epidemiological studies have been conducted to examine the association between MTHFR C677T polymorphism and male infertility susceptibility, but the results remain inconsistent. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 10 case-control studies, including 2275 cases and 1958 controls, were selected. Crude odds ratios (ORs) with 95% confidence intervals were used to assess the strength of association in the additive model, dominant model and recessive model. In the overall analysis, no significant association between the polymorphism and risk of male infertility was observed. Stratified analysis showed that significantly strong association between MTHFR C677T polymorphism and male infertility were present only in Asians (OR = 1.79 for TT vs. CC genotype; OR = 1.42 for CT/TT vs. CC genotype; OR = 1.50 for TT vs. CC/CT genotype; OR = 1.36 for T vs. C allele), but not in Caucasians. Additionally, MTHFR 677T was associated with a significant increase in the risk of azoospermia in all genetic models. No significantly increased risks of oligoasthenoteratozoospermia were found in any of the genetic models. In conclusion, this meta-analysis supports that MTHFR C677T polymorphism is capable of causing male infertility susceptibility in Asians, but not in Caucasians.     

T-786C polymorphism of the endothelial nitric oxide synthase gene is associated with albuminuria in the diabetes heart study

Albuminuria demonstrates significant heritability in multiply affected hypertensive and diabetic families. The role of endothelial nitric oxide synthase (eNOS) gene variants as risk factors for albuminuria was investigated in 590 European American siblings from 230 families in the Diabetes Heart Study. Two polymorphisms in the eNOS gene (T-786C in the promoter region and Glu298Asp in exon 7) were genotyped. Albuminuria was defined as an albumin:creatinine ratio (ACR) >/=17 mg/g in men and >/=25 mg/g in women. Tests of association were based on generalized estimating equations, and tests of linkage disequilibrium were based on the quantitative pedigree disequilibrium test. A total of 83% of participants had type 2 diabetes. The median ACR was 10.7 mg/g (interquartile range, 5.1 to 32.8), and 34% (202 of 590) of participants had an elevated ACR. The eNOS -786C allele but not the Glu298Asp was associated with increased ACR (31% increase in absolute level of ACR for each additional copy of the -786C allele; P < 0.0001) and a higher risk for albuminuria (odds ratio, 1.55 for each additional copy of the -786C allele; P = 0.0005). Adjustment for the nongenetic determinants of ACR had no significant effect on the results; neither did stratification by gender, presence of diabetes, and the Glu298Asp genotype. Results were confirmed by quantitative pedigree disequilibrium test analysis and were consistent with haplotype analysis. The -786C eNOS variant was positively correlated with a higher prevalence and a greater degree of albuminuria in European American families in both diabetic and nondiabetic family members.