Association of AGT M235T gene polymorphism with HSP/HSPN risk

Abstract

To evaluate the association between angiotensinogen (AGT) gene polymorphism and the risk of Henoch–Schönlein purpura (HSP)/Henoch–Schönlein purpura nephritis (HSPN) we searched the eligible studies through Pub Med, Embase, Cochrane, and China National Knowledge Infrastructure (CNKI) databases according to predefined criteria. A random-effects model was used to calculate the combined odds ratios (ORs) and its corresponding 95% confidence interval (CI). Five studies were recruited for the analysis of the association between AGT M235T gene polymorphism and HSP/HSPN risk. M allele was associated with lower risk of HSP in adult (p?=?0.050), TT genotype was associated with the susceptibility to HSP in adult (p?=?0.039). AGT M235T gene polymorphism was not associated with HSP risk in children. No marked association was observed between AGT M235T gene polymorphism and HSPN risk. No evidence of publication bias was observed. In conclusion, M allele might be a protective factor against the HSP risk in adult, TT genotype might be a risk factor for the susceptibility to HSP in adult. However, further larger studies should be performed in the future.     

Angiotensinogen gene M235T polymorphism is not associated with diabetic nephropathy

BACKGROUND.: There is agreement that a family history of hypertension (HT),is a predictor for the risk of diabetic nephropathy (DN) inpatients with type 2 diabetes, and possibly also type 1 diabetes.It follows that genes related to the risk of hypertension mustalso be considered candidate genes for DN. The 235T allele ofthe angiotensinogen gene was found to be related to primaryHT. METHODS.: To examine whether it is predictive for DN as well, we examinedthe angiotensinogen gene polymorphism in 230 healthy local controls,423 patients with type 1 diabetes (n=180 with DN; n=243 withoutDN) and 663 patients with type 2 diabetes (n=310 with DN; n=353without DN). The angiotensinogen gene M235T polymorphism wasdetermined using PCR amplification. RESULTS.: The following results were obtained (i) no significant differenceof genotype distribution (type 1: MM/MT/TT(%) 27.6/57.2/15.2vs. 27.2/56.1/16.7 (P=0.92); type 2: MM/MT/TT (%) 31.7/48.2/20.1vs. 32.9/46.8/20.3 (P=0.93)) or allele frequencies (type 1:M 0.56 vs. 0.55 (P=0.795); type 2: M 0.56 vs. 0.56 (P=0.86))was found, between diabetic patients with or without DN, (ii)no difference was found between normotensive and hypertensivediabetic patients. CONCLUSION.: The data argue against a role of the angiotensinogen gene M235Tpolymorphism in the manifestation of diabetic nephropathy orhypertension in diabetic patients.     

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.     

Association of the methylenetetrahydrofolate reductase gene C677T polymorphism with the risk of male infertility: a meta-analysis

Several molecular epidemiological studies have been conducted to examine the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and male infertility susceptibility, but the results remain inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. In this meta-analysis, a total of 26 case–control studies including 5659 infertility cases and 5528 controls were selected to evaluate the possible association. The pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were used to assess the strength of association of C677T polymorphism with male infertility in the additive model, dominant model, recessive model and allele-frequency genetic model. In the overall analysis, the frequency of the 677T allele was significantly associated with male infertility susceptibility (OR?=?2.32, 95%CI?=?2.04–2.65 for TT vs. CC genotype; OR?=?1.09, 95%CI?=?1.00–1.19 for CT vs. CC genotype; OR?=?1.19, 95%CI?=?1.10–1.29 for CT/TT vs. CC genotype; OR?=?1.54, 95%CI?=?1.36–1.74 for TT vs. CC/TT genotype; OR?=?1.22, 95%CI?=?1.15–1.30 for T vs. C allele). A subgroup analysis of the subjects showed that significantly strong association between MTHFR C677T polymorphism and male infertility was present only in Asians, but not in Caucasians. Additionally, MTHFR C677T was associated with a significant increase in the risk of azoospermia in all genetic models. Meanwhile, no significantly increased risks of oligoasthenotertozoospermia (OAT) were found in most of the genetic models. In conclusion, this meta-analysis is in favor that the MTHFR C677T polymorphism is capable of causing male infertility susceptibility, especially in Asians and the subgroup of azoospermia.     

Association of angiotensin-converting enzyme insertion/deletion polymorphism with type 1 diabetic nephropathy: a meta-analysis

Objective: This study aimed to systematically evaluate the effect of an angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism on type 1 diabetic nephropathy (DN).

Methods: Cochrane Library, Embase, PubMed, Science Direct, Web of science, Wanfang data, VIP database, China Knowledge Resource Integrated Database, and SinoMed were searched. A total of 17 case–control studies analyzing ACE I/D polymorphism and type 1 DN risk were included in the present meta-analysis.

Results: Overall, a significant increased risk was found in allele comparison (OR?=?1.16, 95% CI?=?1.05–1.28, p?=?0.04), dominant comparison (OR?=?1.56, 95% CI?=?1.14–2.15, p?=?0.006) and homozygote comparison (OR?=?1.52, 95% CI?=?1.06–2.19, p?=?0.02). In subgroup analyses according to ethnicity, the risk of type 1 DN in Asian population was increased in allele comparison (OR?=?1.98, 95% CI?=?1.15–3.42, p?=?0.01), recessive comparison (OR?=?2.48, 95% CI?=?1.51–4.10, p?=?0.0004), dominant comparison (OR?=?3.15, 95% CI?=?1.90–5.23, p?p?=?0.05). However, there was no association between the ACE I/D genetic variants and type 1 DN in Caucasian populations.

Conclusions: Our meta-analysis results indicate that the ACE I/D polymorphism may contribute to type 1 DN development, especially in the Asian groups with type 1 diabetes. The current findings need to be confirmed by future well-designed and larger sample size primary studies in populations with different ethnicities.     

The ACACB gene rs2268388 polymorphism is associated with nephropathy in Caucasian patients with diabetes: a meta-analysis

Abstract

To date, case–control studies on the association between a single-nucleotide polymorphism (SNP), rs2268388, in the acetyl-coenzyme A carboxylase beta (ACACB) gene and diabetic nephropathy have provided controversial results. To clarify the effect of rs2268388 on the risk of diabetic nephropathy, a meta-analysis of all case–control studies was performed. The fixed effects and random effects models showed that the C allele was associated with a decreased susceptibility risk of diabetic nephropathy compared with the T allele among Caucasian patients with diabetes. The contrast of the recessive model produced the same pattern of results as the allele contrast. Our pooled data suggest a significant association exists between rs2268388 and diabetic nephropathy among Caucasian patients with diabetes.     

Relationship between methylenetetrahydrofolate reductase (MTHFR) A1298C gene polymorphism and type 2 diabetic nephropathy risk: a meta-analysis

Relationship between methylenetetrahydrofolate reductase (MTHFR) A1298C gene polymorphism and type 2 diabetic nephropathy (T2DN) risk is still unclear. This study was performed to evaluate if there is an association between the MTHFR A1298C gene polymorphism and T2DN risk using meta-analysis. The relevant reports were searched and identified from PubMed, Cochrane Library on 1 October 2013, and eligible studies were included and synthesized. Eight reports were recruited into this meta-analysis for the association of the MTHFR A1298C gene polymorphism with T2DN risk. The MTHFR A1298C C allele or CC genotype was shown to be not associated with T2DN risk (C allele: OR?=?0.76, 95% CI: 0.43–1.34, p?=?0.34; CC genotype: OR?=?1.18, 95% CI: 0.63–2.22, p?=?0.60). Interestingly, AA genotype was associated with the T2DN risk (OR?=?0.68, 95% CI: 0.49–0.96, p?=?0.03). In the sensitivity analysis according to the Hardy–Weinberg equilibrium (HWE), the results were consistent with those in non-sensitivity analysis. However, in the sensitivity analysis according to the control source from hospital, sample size of case (≥100), sample size of case (<100), the MTHFR A1298C gene polymorphism was not associated with T2DN risk. In conclusion, the MTHFR A1298C gene polymorphism was not associated with T2DN risk. However, additional studies are required to firmly establish a correlation between the MTHFR A1298C gene polymorphism and T2DN risk.     

Association between the RAGE gene -374T/A, -429T/C polymorphisms and diabetic nephropathy: a meta-analysis

Abstract

Aim: The investigations into the association between the receptor for advanced glycation end products (RAGE) gene -374T/A, -429T/C polymorphisms and diabetic nephropathy (DN) in several case–control studies have rendered conflicting results. To shed light on these inconclusive findings, a meta-analysis of all the eligible studies relating these two polymorphisms to the risk of DN was conducted. Methods: The databases were searched for relevant articles up to July 2014. A pooled estimate of the genetic association, the heterogeneity between studies, and the publication bias were investigated. Results: Eight studies with 1725 cases and 1857 controls were enrolled in -374T/A polymorphism analysis. The main analysis indicated no association for the allele contrast, the recessive model and the dominant model. Subgroup analyses in Caucasians and in type 2 diabetes also showed no association between -374T/A polymorphism and DN. Five studies with 1019 cases and 792 controls were enrolled in -429T/C polymorphism analysis. The main analysis revealed heterogeneity and no association for the allele contrast and the dominant model. However, the recessive model for -429C allele diminished the heterogeneity and showed a marginal association overall [fixed-effects OR?=?2.83 (1.33–6.00) and random effects OR?=?2.50 (1.00–6.24), respectively]. Conclusions: Our meta-analysis indicated that the RAGE gene -429CC genotype might be a risk factor for DN in patients with type 2 diabetes.     

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.     

The SPO11-C631T gene polymorphism and male infertility risk: a meta-analysis

To evaluate the association between the SPO11 gene C631T polymorphism and the risk of male infertility. We conducted a search on PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), China biology medical literature database (CBM), VIP, and Chinese literature database (Wan Fang) on 31 March 2016. Odds ratio (OR) and 95% confidence interval (95%CI) were used to assess the strength of associations. A total of five studies including 542 cases and 510 controls were involved in this meta-analysis. The pooled results indicated that the SPO11 gene C631T polymorphism was significantly associated with increased risk of male infertility (TT?+?CT vs. CC: OR?=?4.14, 95%CI?=?2.48–6.89; CT vs. CC: OR?=?4.34, 95%CI?=?2.56–7.34; T vs. C: OR?=?4.35, 95%CI?=?2.58–7.34). Subgroup analysis of different countries proved the relationship between SPO11 gene C631T polymorphism and male infertility risk in Chinese, but not in Iranian peoples. In conclusion, this study suggested that SPO11 gene C631T polymorphism may contribute as a genetic factor susceptible to cause male infertility. Furthermore, more large sample and representative population-based cases and well-matched controls are needed to validate our results.     

Monocyte chemoattractant protein-1 -2518G/A gene polymorphism and the risk of nephropathy in type 2 diabetes mellitus among Asians: a meta-analysis

The association between monocyte chemoattractant protein-1 (MCP-1) -2518G/A gene polymorphism and the risk of nephropathy in type 2 diabetes mellitus (T2DM) remains controversial. A meta-analysis was conducted to assess the association of MCP-1 -2518G/A gene polymorphism with the risk of nephropathy in T2DM. Eight studies were included in our meta-analysis by searching electronic databases according to predefined criteria. No significant association between G allele, GG genotype, or AA genotype and the onset of nephropathy in T2DM was observed among Asians. GA genotype was significantly associated with nephropathy risk in T2DM among Asians (p?=?0.024). MCP-1 -2518G/A gene polymorphism was not associated with nephropathy risk in T2DM among Chinese, Koreans, and Turks. For Indians, G allele and AA genotype were not associated with nephropathy risk in T2DM, GG genotype was associated with a lower risk of nephropathy in T2DM (p?=?0.017), GA genotype was associated with the susceptibility of nephropathy in T2DM (p?=?0.029). In conclusions, GA genotype might be a risk factor for the onset of nephropathy in T2DM among Asians, particularly Indians; GG genotype seems to be a protective factor against the susceptibility of nephropathy in T2DM among Indians.     

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and susceptibility to diabetic nephropathy in Chinese type 2 diabetic patients: a meta-analysis

Abstract

The association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and diabetic nephropathy (DN) or diabetes mellitus (DM) risk has been widely reported, but the results are still debatable. To investigate the role of MTHFR C677T polymorphism on DM or DN, 13 separate studies in the Chinese population on the relation between MTHFR C677T polymorphism and DM or DN were analyzed by a meta-analysis. Five genetic models were used to estimate the association between MTHFR C677T polymorphism and the risk of DM or DN. Overall, our meta-analysis for DN versus healthy controls produced significant results for all genetic contrasts except for the co-dominant model (allele contrast: OR?=?2.24, 95%CI: 1.88–2.65, p?<?0.00001, P_{heterogeneity}?=?0.49). However, the meta-analysis for DM versus healthy controls produced non-significant results for all contrasts (allele contrast: OR?=?1.12, 95%CI: 0.92–1.35, p?=?0.25, P_{heterogeneity}?=?0.07). In addition, the meta-analysis for DM versus DN produced significant results for all contrasts (allele contrast: OR?=?1.88, 95%CI: 1.65–2.15, p?<?0.00001, P_{heterogeneity}?=?0.83). The current meta-analysis suggested that MTHFR C677T polymorphism might influence DN risk, but not for DM in the Chinese population.     

Lack of association between NPHS2 gene polymorphisms and sporadic IgA nephropathy

AIM: IgA nephropathy (IgAN) is the most common primary form of glomerulonephritis worldwide. In the present study, the genetic structure of the NPHS2 gene was studied to verify if podocin plays a role in the pathogenesis of IgAN. METHODS: Clinical characteristics and DNA samples were collected from 26 Chinese children with sporadic IgAN. A direct sequencing was performed after polymerase chain reaction amplification to all the eight exons of the NPHS2 gene. RESULTS: Three synonymous variants as known polymorphisms (954T-->C homozygous, 1038A-->G heterozygous and homozygous) were found in 3, 4 and 1 patients, respectively. There was no significant difference in the genotypic and allelic frequencies of 954T > C and 1038A > G polymorphisms between the patients and normal controls. CONCLUSION: No significant difference in the genotypic and allelic frequencies of the identified 954T > C and 1038A > G polymorphisms between the patients and normal controls was found.     

Hydroxychloroquine in IgA nephropathy: a systematic review

BackgroundHydroxychloroquine (HCQ) has recently been reported to be a promising and safe anti-proteinuric agent for IgA nephropathy (IgAN) patients. In the present systematic review, we aimed to summarize the evidence concerning the benefits and risks of HCQ therapy in IgAN.MethodsElectronic databases were searched for randomized, cohort, or case-control studies with IgAN biopsy-proven patients comparing the effects of HCQ with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers or immunosuppression on proteinuria reduction.ResultsFive studies, one randomized and three observational, involving a total of 504 patients, were eligible for inclusion. Overall, there was a tendency of HCQ treatment to reduce proteinuria. In the studies where the control arm was supportive therapy, HCQ significantly reduced proteinuria at 6 months. However, in the studies that compared HCQ to immunosuppressive therapy, we found no difference in proteinuria reduction. HCQ had no impact on eGFR.ConclusionHCQ seems to be an efficient alternative therapy for patients with IgAN who insufficiently respond to conventional therapy. However, ethnically diverse randomized controlled studies with long-term follow-up are needed.     

Adiponectin gene polymorphisms and susceptibility to diabetic nephropathy: a meta-analysis

Adiponectin (ADIPOQ) plays an important role in the pathogenesis of diabetic nephropathy (DN) and previous studies regarding the association between ADIPOQ polymorphisms and DN risk reported conflicting results. To derive a more precise estimation of this association, we performed a meta-analysis to assess the association between four ADIPOQ polymorphisms [?11391G?>?A (rs17300539), ?11377C?>?G (rs266729), +45T?>?G (rs2241766), and +276G?>?T (rs1501299)] and risk for DN. Odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) were pooled to assess the association between four aforementioned polymorphisms and susceptibility to DN. Based on the included criteria, we selected 13 articles, among which 7 studies (cases/controls: 2749/7585) for ?11391G?>?A, 8 studies for ?11377C?>?G (3074/3842), 9 studies for +45T?>?G (2654/7710), and 10 studies for +276G?>?T (2812/7821), respectively. Our meta-analysis indicated no evidence heterogeneity among the included studies; thus, the fixed-effects model was used. Overall, there was an association between ADIPOQ ?11391A allele with increased DN risk (OR?=?1.186, 95% CI: 1.051–1.338, p?=?0.006). Subgroup by ethnicity suggested significant association between +45T?>?G polymorphism and DN risk among Caucasians (OR?=?1.122, 95% CI: 1.007–1.250, p?=?0.038). Sensitivity analysis suggested exclusion of any single study did not materially alter the overall pooled ORs above. Future studies are needed to validate these findings.     

Polymorphisms of renin-angiotensin system genes in childhood IgA nephropathy

We investigated whether polymorphisms of the renin-angiotensin system genes are involved in IgA nephropathy in Japanese children. We identified the M235T polymorphism of the angiotensinogen (AGT) gene, the I/D polymorphisms of the angiotensin-converting enzyme (ACE) gene, and the A1166C polymorphism of the angiotensin II type 1 receptor gene in 95 Japanese children with IgA nephropathy and 99 healthy Japanese adults. There were no differences in the genotype and allele frequencies of these genes between patients with IgA nephropathy and controls. Urinary protein excretion at the time of biopsy was significantly greater in patients with the TT genotype of the AGT gene than in those with the MM/MT genotypes of the AGT gene (1.32± 1.42 versus 0.75±0.78 g/day; P=0.01) and in patients with the ID/DD genotypes of the ACE gene than in those with the II genotype of the ACE gene (1.45±1.50 versus 0.63±0.56 g/day; P=0.001). Thus, the TT genotype of the AGT gene and the ID/DD genotype of the ACE gene are associated with increased severity of proteinuria, suggesting that AGT and ACE gene polymorphisms may play a significant role in the progression of IgA nephropathy in Japanese children. Received: 21 July 2000 / Revised: 8 December 2000 / Accepted: 11 December 2000