Association of Methylene Tetrahydrofolate Reductase C677T Genotype With Type 2 Diabetes Mellitus Patients With and Without Renal Complications

Abstract

Diabetes is gradually getting the status of a global epidemic, with India projected as the capital of type 2 diabetes mellitus (T2DM). Nephropathy is an important complication of diabetes and a major cause of end-stage renal disease. Studies from different parts of the world have given controversial results regarding the association of methylene tetrahydrofolate reductase (MTHFR) gene variation with T2DM and diabetic nephropathy (DN). This case-control study assessed the association of MTHFR C677T mutation in T2DM and DN cases. Genotyping of MTHFR was carried out for 236 T2DM cases with diabetes diagnosed for >8 years, having either normoalbuminuria (n=100) or established DN (n=136). One hundred age- and sex-matched healthy individuals with normal blood sugars and no family history of T2DM were selected as controls. This first report from India gives a highly significant odds ratio of 4.0423 (95% confidence interval=1.8753-8.7133), indicating that the MTHFR 677T allele confers a fourfold risk of developing DM in our population. The frequency of the T allele in both the DM and DN groups was similar (i.e., 0.16 and 0.11, respectively), showing no association with the initiation or progression of DN. Individuals with a family history of diabetes or with risk factors such as obesity, hypertension, and impaired glucose tolerance should be screened for MTHFR C677T mutation and may be prescribed folic acid, vitamin B6, and vitamin B12 to assess if this helps in delaying the onset of diabetes.

Additive Interaction of MTHFR C677T and MTRR A66G Polymorphisms with Being Overweight/Obesity on the Risk of Type 2 Diabetes

“…The relationship between the MTHFR C677T polymorphism and T2D risk has been explored in many previous studies, with some indicating positive association [5,7,22,26], whereas others reported null association [21,23,24,25]. A number of factors may contribute to the discrepancy between prior studies, such as ethnic genetic differences and dietary habits.…”

“…Cooccurrence with the MTRR A66G polymorphism may aggravate the adverse effect of the MTHFR C677T polymorphism on plasma Hcy level [20]. Some studies have assessed the relationship between the MTHFR C677T polymorphism and T2D, with most showing a significant positive association [5,7,21,22,23,24,25,26]. Mechanisms linking HHcy with T2D are not clearly understood, and one of them may be insulin resistance [27,28].…”

MTHFR 677C/T and 1298A/C mutations and non-alcoholic fatty liver disease

“…22 Movva et al determined that the MTHFR C677T allele confered a four-fold risk of developing type-2 diabetes mellitus in their study on 236 diabetic patients and 100 control individuals. 23 An increase in mean serum Hcy concentrations in women with polycystic ovarian syndrome, another clinical condition associated with insulin resistance, has also reported. 24 In addition, Schachter et al previously reported that insulin resistance and hyperinsulinaemia in patients with PCOS is associated with elevated plasma Hcy levels regardless of body weight.…”

Evaluation of an association of the rs1801133 MTHFR gene polymorphism with folic acid deficiency in obese patients

“…В этой связи отметим, что в исследовании, проведенном по типу «случай -контроль» в Китае и Индии, была выявлена ассоциация аллеля Т это-го полиморфизма с высоким уровнем гомоцистеи-на, сахарным диабетом 2-го типа и нефропатоло-гией, осложняющей течение данного заболевания [6][7][8][9].…”

“…Результаты популяционных исследований по-казали, что полиморфизм rs1801133 гена MTHFR ассоциирован с увеличением риска формирова-ния дефекта нервной трубки у плода, развития сердечно-сосудистых заболеваний, сахарного диа-бета 2-го типа и остеопороза [6][7][8][9]. Частота встре-чаемости аллеля Т в европейских популяциях со-ставляет 30-33% [6,10].…”