title: Interaction of MTHFR 1298C with ACE D allele augments the risk of diabetic nephropathy in Western Iran.
abstract: The aim of the current study was to examine the influence of interaction between polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C with angiotensin converting enzyme insertion/deletion (ACE I/D) polymorphism on the risk of diabetic nephropathy (DN). In a case control study using polymerase chain reaction (PCR)- and PCR-restriction fragment length polymorphism (RFLP), the presence of three polymorphisms in 140 patients with type 2 diabetes mellitus (T2DM) with nephropathy including patients with micro- and macro-albuminuria and 72 patients with normoalbuminuria from Western Iran were investigated. In the presence of both MTHFR 677 T and ACE D alleles, there was a trend toward increased risk of DN 2.68-fold (p=0.054). The possession of both MTHFR 677 T and ACE D alleles increased the risk of macro-albuminuria four times (p=0.035). The concomitant presence of both MTHFR 1298 C and ACE D alleles increased the risk of macro-albuminuria 7.8-fold (p=0.012). In addition, the risk of progression from micro- to macro-albuminuria in the presence of both alleles tended to be increased (4.1-fold, p=0.09). Our study for the first time demonstrated a synergistic effect between ACE I/D with either MTHFR C677T or A1298C polymorphism on the increased risk of DN among patients with T2DM. We found that MTHFR 1298 C strongly interacts with the ACE D allele and augments the risk of DN in our population.
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran. zrahimi@kums.ac.ir
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Rahimi
authors.forename: Ali
authors.initials: A
authors.lastname: Hasanvand
authors.forename: Vahid
authors.initials: V
authors.lastname: Felehgari
mesh_terms: D000419:Albuminuria / Q000453:epidemiology / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007492:Iran / Q000453:epidemiology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors
chemical_list: D017931:DNA Primers; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A