Assessment of mitochondrial DNA ND2 gene C5178A polymorphism for cerebral-cardiovascular complications in patients with type 2 diabetes mellitus

Abstract

Objective To assess the relationship between mitochondrial DNA (mtDNA) ND2 gene C5178A polymorphism and complications of cardio-cerebral-vascular in patients with type 2 diabetes mellitus (T2DM). Methods This is a case-control study.448 unrelated patients with T2DM were collected from Zhejiang Provincial People′s Hospital from 2010 to 2011,including 274 males and 174 females.Direct nucleotide sequencing analysis was used to screen mt DNA ND2 gene C5178A genotyping in patients.Meanwhile,detailed clinical and laboratory information for all of study subjects were collected.Body mass index (BMI),blood pressure,blood lipid,blood glucose and incidence rate of cerebral infarction were compared between 5178C patients and 5178A patients.Furthermore,according to the genotyping results,we analyzed whether these differences exist in patients with different gender by using t test or χ2test. Results 348 out of 448 patients with T2DM were C carriers and the remaining patients were A carriers.There′re significant differences between T2DM patients with 5178A and T2DM patients with 5178C on systolic pressure (124.6 mm Hg±9.0 mm Hg vs 127.8 mm Hg±10.7 mm Hg,t=2.700,P=0.007) and HDL (1.3 mmol/L±0.2 mmol/L vs 1.2 mmol/L±0.3 mmol/L,t=2.968,P=0.003).Moreover,the incidence of cerebral infarction in T2DM patients with 5178A (8.0%,8/100) was much lower than that with 5178C (21.0%,73/348; χ2=8.832,P=0.003).No statistical gender difference was found in the distribution of C5178A (P>0.05).Our results also revealed that the female T2DM patients with 5178A had a lower serum triglyceride (1.5 mmol/L±0.8 mmol/L; t=2.601,P=0.011) and lower systolic pressure (123.6 mm Hg±6.6 mm Hg;t=2.887,P=0.004) than that with 5178C (1.8 mmol/L±1.0 mmol/L and 128.0 mm Hg±9.0 mm Hg, respectively).Furthermore,cerebral infarction was more common in female T2DM patients with 5178C (21.3%,29/136;χ2=5.232,P=0.022) than that with 5178A (5.3%,2/38).Similarly,male T2DM patients with 5178A had a much lower incidence rate of cerebral infarction (9.7%,6/62;χ2=3.946,P=0.047) than that with 5178C (20.7%,44/212).In contrary, the serum concentration of HDL was higher in male T2DM patients with 5178A (1.4 mmol/L±0.2 mmol/L; t=3.511,P=0.001) than that with 5178C (1.2 mmol/L±0.3 mmol/L). Conclusions The polymorphism site mtDNA C5178A correlates with cerebral-cardiovascular complications in patients with type 2 diabetes mellitus.mt DNA 5178A allele may protect T2DM patients from developing cerebral-cardiovascular diseases through regulation of blood pressure and lipid metabolism.(Chin J Lab Med,2013,36:519-522) Key words: Diabetic angiopathies; Diabetes mellitus; type2; Brain infarction; NADH dehydrogenase; DNA; Mitochondrial; Polymorphism; genetic