MTHFR C677T, A1298C and ACE I/D polymorphisms as risk factors for diabetic nephropathy among type 2 diabetic patients

Elbaz, Rizk; Settin, Ahmad; Ismaeel, Azza; Khaleel, Abd Allah; Abbas, Tarek M.; Tolba, Wafaa; Allah, Wafaa A; Sobh, Mohamed

doi:10.1177/1470320312444651

Cited by 28 publications

(25 citation statements)

References 56 publications

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“…Thus, the contribution of ACE gene polymorphism to the heritable part of risk for diabetic nephropathy seems important, and is supported by findings from published meta-analyses [28,62] along with other studies done among Indians [31,63], Japanese [29], French [64], Egyptian [65] and Taiwan [27] diabetic patients. However, our results do not coincide with studies done among Chinese [66], Tunisian [55], French [56], Turkish [34] and Iranian [67] diabetic cases.…”

Section: Discussionsupporting

confidence: 54%

Genetic Predisposition to Diabetic Nephropathy: Evidence for a Role of ACE (I/D) Gene Polymorphism in Type 2 Diabetic Population from Kutch Region

et al. 2013

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Genetic polymorphism as described with angiotensin-converting enzyme gene has been proposed as a putative mediator of diabetic nephropathy. We substantiate the hypothesis that genetic variants of the ACE have significant impacts on diabetic nephropathy. To assess the possible association between the three ACE polymorphic variants and DN in an ethnically homogeneous type 2 diabetic population from Kutch region. A 287-bp insertion/deletion polymorphism in intron 16 of the ACE gene was examined by polymerase chain reaction using a case-control approach conducted with 309 unrelated type 2 diabetic patients of Kutch origin (159 Ahir and 150 Rabari, with [10 years duration of T2DM). Of the patients, 143 had nephropathy {AER[30 mg/day (Ahir, n:73 and Rabari, n:70)} and were considered as cases; all others {n:166 (86 Ahir and 80 Rabari)} were normoalbuminuric (AER\30 mg/day) and were treated as controls. Suitable descriptive statistics was used for different variables. Genotype frequencies in all groups were all in accordance with the Hardy-Weinberg equilibrium. Genotypic distribution was significantly different between cases and controls (Ahir: x 2 :8.87, 2 d.f. p = 0.0118; Rabari: x 2 :11.01, 2 d.f. p = 0.0041). Multivariate logistic regression analysis revealed that DD genotype was a significant and strongest independent predictor of microalbuminuria (Ahir: p = 0.0362, OR = 2.65, 95 % CI 1.89-6.36; Rabari: p = 0.024, OR = 2.81, 95 % CI 1.9-6.65). However, it did not independently change the odds of having macroalbuminuria versus microalbuminuria. Analysis of the association under various genetic models revealed that ACE I/D polymorphic variant contribute to DN susceptibility under recessive mode only. Genetic variation at the ACE locus as D/D variant in intron 16, contribute to an increased risk of nephropathy in T2DM patients but not extent of DN severity, and thus this polymorphism might be considered as genetic risk factors for DN among patients with type 2 diabetes.

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Section: Discussionsupporting

confidence: 54%

Genetic Predisposition to Diabetic Nephropathy: Evidence for a Role of ACE (I/D) Gene Polymorphism in Type 2 Diabetic Population from Kutch Region

et al. 2013

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“…3 Deficiency of MTHFR may be associated with the levels of plasma folate and homocysteine metabolism, which in turn is associated with an increased risk of vascular diseases including the predisposition to nephropathy among diabetic patients. 4 The present evidence indicates that A1298C polymorphism is associated with the risk of type 2 diabetic nephropathy (T2DN). 3 Diabetic nephropathy (DN) is one of the most serious microvascular complications of diabetes mellitus, and is the primary cause of end-stage renal disease (ESRD) worldwide.…”

Section: Introductionmentioning

confidence: 88%

“…Eight studies 4,[15][16][17][18][19][20][21] reporting the relationship between MTHFR A1298C gene polymorphism and T2DN susceptibility were recruited into this meta-analysis. The data of our interest were extracted (Table 1) and the included investigations contained 1387 patients with T2DN and 1533 controls.…”

Section: Study Characteristicsmentioning

confidence: 99%

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

Zhang¹,

Xiao²,

Zhang

et al. 2014

Renal Failure

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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 (5100), 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.

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“…This low frequency might not necessarily reflect a lower occurrence of the polymorphism in this particular ethnic group, but might be a result of the small sample size. Furthermore, the data collected originated from patients geographically restricted to northern Africa 49 and by no means reflected an ethnic cross-section of the whole continent. Nonetheless, a new principle finding can equally not be ruled out, but will require further prospective studies in Africans with various ethnic and geographic backgrounds.…”

Section: Discussionmentioning

confidence: 99%

“…49 The data of interest were extracted, as summarized in Table 1. In total, the 33 investigations contained 3959 DN patients and 3915 controls.…”

Section: Study Characteristicsmentioning

confidence: 99%

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

Zhou

Drummen²,

Jiang

et al. 2015

Renal Failure

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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: p50

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MTHFR C677T, A1298C and ACE I/D polymorphisms as risk factors for diabetic nephropathy among type 2 diabetic patients

Abstract: These findings indicate that ACE and MTHFR genetic polymorphisms might be considered as genetic risk factors for diabetic nephropathy among patients with type 2 diabetes.

Cited by 28 publications

References 56 publications

Genetic Predisposition to Diabetic Nephropathy: Evidence for a Role of ACE (I/D) Gene Polymorphism in Type 2 Diabetic Population from Kutch Region

Genetic Predisposition to Diabetic Nephropathy: Evidence for a Role of ACE (I/D) Gene Polymorphism in Type 2 Diabetic Population from Kutch Region

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

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

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