| Background and ObjectivesAldose reductase (AR), a member of aldo-keto reductase superfamily, is a monomeric reduced nicotinamide adenine dinucleotid phosphate(NADPH)-dependent enzyme. AR can catalyze a variety of hydrophilic aldehydes (including aldehyde form of glucose) to corresponding alcohols.AR is characterized as a rate-limiting enzyme in the polyol pathway of glucose metabolism. In the state of long-term high blood glucose, AR activity is increasing. The metabolism of glucose in the polyol pathway increases, which is of importance as a risk factor leading to nephropathy, retinopathy, neuropathy and atherosclerosis process and ischemic myocardial injury in diabetic patients. The gene mutation which caused abnormal expression and the activity alternation may be a pathogenic cause.This study aims to investigate AR C(-106)T polymorphism and the genotypes distribution frequencies characteristics in Han Nationality population in Northern China and its effects on blood glucose, lipid levels and its relationship with type 2 diabetes, coronary heart disease, type 2 diabetes combined with coronary heart disease, so as to provide scientific data for prevention and control of atherosclerotic coronary heart disease.Subjects and MethodsThe genotypes of AR C(-106)Twere analyzed by polymerase chain reaction(PCR) and restriction fragment length polymorphism(RFLP) in the samples of 125 unrelated healthy individuals as control group,85 patients with type 2 diabetes mellitus (DM group),91 patients with coronary heart disease (CHD group) and 78 diabetic patients with coronary heart disease (DM+CHD group) in Han nationality from Northern China. Serum total cholesterol (TC) and triglyceride (TG) were measued with standard enzymatic assay. Serum high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) were determined with homogeneous method. Blood glucose (Glu) was measured with glucose oxidase method and hemoglobin Alc(HbAlc) with high performance liquid chromatography (HPLC). Excel 2007 and SPSS 18.0 were used for data processing and statistical analysis.Results1. BMI, Glu, TG levels in DM group, CHD group and DM+CHD group were significantly higher than the control group, while the average level of HDL-C was lower than the control group.2. The incidence of hypertension in DM+CHD group was higher than DM group, but BMI, HbAlc, Glu, TC, HDL-C, LDL-C levels were lower than the DM group. The incidence of hypertension in DM+CHD group was higher than CHD group and HbAlc, Glu levels were also higher than CHD group.3. AR C(-106)T gene polymorphisms of CC, CT, TT and C, T alleles frequencies distribution in the control group were 59.2%,39.2%,1.6%,78.8%,21.2% respectively; 69.4%and 27.1%,3.5%,82.9%,17.1%in DM group and 73.6%,22.0%, 4.4%,84.6%,15.4%in CHD group and 67.9%,30.8%,1.3%,83.3%,16.7%in DM+CHD group.4. AR C(-106)T genotypes frequency distribution of CC, CT, TT in all subjects were 66.8%,30.6%,2.6%, and the alleles C, T were 82.1%,17.9%. The frequencies distribution of AR C(-106)T genotypes and alleles between this study and Japanese, Tianjin China showed no significant difference, but significantly different when compared with Qingdao China, Brazil, Poland studies. 5. Compared with the control group, AR C(-106)T gene polymorphism of the three kinds of genotypes of CHD group were significantly different; DM group, DM+ CHD group showed no significant difference. C, T allele frequency distribution showed no statistical difference in all groups.6. There were no significant differences in the distribution of AR C(-106)T gene polymorphisms of CC, CT, TT genotypes in men and women. C, T alleles distribution showed the same result with genotypes when compared between men and women.7. The Glu level of individuals with CC genotype in DM group was significantly higher than the individuals with CT+TT genotypes in the same group. Other indicators such as BMI, HbAlc, TC, TG, HDL-C, LDL-C showed no significant difference in different genotypes. There were no statistical difference between individuals with CC and CT+TT genotypes in other three groups8. There was no significant correlation between the genotype and the level of Glu or HbAlc. There was no significant correlation between the genotype and the diseases. AR C(-106) T polymorphisms may not independent risk factors in diabetes, coronary heart disease and diabetes mellitus combined with coronary heart disease.ConclusionIn this study, we developed the method of genome DNA extractin by sodium iodide (Nal) and analysis of AR C(-106)T gene polymorphisms by PCR-RFLP. The method is simple and fast, easy to operate, suitable for large-scaled epidemiological investigation and clinical study in laboratory.There were no difference of the frequencies distribution of AR C(-106)T genotypies and C, T alleles among normal individuals, patients with diabetes, coronary heart disease, diabetes combined with coronary heart disease, and also the same between men and women.AR C(-106)T CC genotype and C allele may be risk factors of poor glycemic control in patients with DM. AR C(-106)T gene polymorphisms may not independent risk factors for diabetes mellitus, coronary heart disease and diabetes combined with coronary heart disease. |
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