Prevalence of methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in Egyptian patients with type 2 diabetes mellitus

Abstract EN

Type 2 diabetes mellitus (T2DM) is a major public health problem around the world.

The C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene have been reported to be associated with T2DM and its complications.

This study is a casecontrol study which was performed to clarify the association between polymorphisms in these two genes and T2DM among Egyptians.

Study population (n = 120) consists of 60 Egyptian diabetic patients and 60 healthy controls.

The MTHFR C677T and A1298C polymorphisms were genotyped by polymerase chain reaction, followed by enzymatic digestion with HinfI and MboII enzymes, respectively.

C677T and A1298C genetic polymorphisms conveyed an increase in T2DM risk (OR = 3.5, 95 % CI = 1.1–11.6, p = 0.032 and OR = 2.2, 95 % CI = 0.7–6.9, p = 0.004 respectively).

Additionally, no significant associations between lipid / glucose metabolic indexes with MTHFR genotypes among diabetic patients were observed.

Combined MTHFR gene polymorphisms revealed higher T2DM risk in homozygous and heterozygous forms compared to single gene polymorphism with pronounced risk in C677T / CT-A1298C / CC combined form (OR = 6.56, 95 % CI = 0.76–56.2, p 0.041).

In conclusion, our data suggest that MTHFR C677T and A1298C polymorphisms are risk factor for T2DM in Egyptian patients.

Also, the two gene polymorphisms may act synergistically to increase the risk of diabetes.

Furthermore, it of Medicine federal number IRB00006444’’, prior to sample collection.

Inclusion criteria: fasting plasma glucose P126 mg / dl, Hemoglobin A1c P6.5 % and / or treatment for diabetes including diet and / or oral antidiabetic drugs to achieve glycemic control.

Duration of the disease on diabetic patients was 7.8 ± 2.1 years.

Recruitment of patients was restricted by the following criteria : the presence of hypertension / or taking antihypertensive drugs, diabetic nephropathy defined by persistent microalbuminuria (Albumin : Creatinine Ratio in spot urine sample : 2.5–25 mg / mmol in males, 3.5– 35 mg / mmol in females) checked at least on two consecutive occasions over the previous 6 months.

Renal or liver failure, retinopathy diagnosed by funduscopy examination, cardiovascular disease and intake of hormonal replacement therapy.

Taking hypoglycemic drugs and lipid lowering drugs were not considered as exclusion criteria.

Detailedmedical history for each group was obtained.

Weight and height were measured to calculate the body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured in a sitting position using a mercury column sphygmomanometer after at least 5 min of rest ; two readings of SBP and BPwere taken.

Using NICE hypertension guideline 2011, standards for hypertension was SBP P140 mmHg and DBP P90 mmHg [21].

Clinical and biochemical measurements of patients with type 2 diabetes were performed after 8 h of fasting.

Diagnosis of diabetes was according to the criteria of American diabetes association (Fasting plasma glucose ; FPG P126 mg / dl.

Fasting is defined as no caloric intake for at least 8 h) [22].

Control subjects did not have any abnormalities regarding their physical examination, blood pressure, family history, urine analysis, and routine laboratory blood tests ; none of them were receiving any medications at the time of participation.