| Objective:To explore the risk factors of diabetic retinopathy and analyze the relationships between diabetic retinopathy and polymorphisms of methylenete-trahydrofolate reductase (MTHFR) gene and aldose ruedctase (AR) gene among the patients with type 2 diabetes mellitus, and provide scientific basis for the prevention of diabetic retinopathy in type 2 diabetic patients.Methods:A hospital-based case-control study was conducted in Tianjin from 2009 June to 2010 October. The subjects included 513 patients with type 2 diabetes mellitus, among which 219 patients with diabetic retinopathy as case group,294 patients without diabetic retinopathy as control group. The information was collected by using self-made questionnaire, which include demographic data, disease history, disease family history, dietetic habit, behavior pattern, social psychologic character, clinical data and laboratory data. Whole blood samples were collected from 161 cases and 213 controls. The polymorphisms of MTHFR gene and AR gene were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The risk factors were analyzed by non-conditional logistic regression and odds ratio (OR) and 95% confidence interval (CI) were calculated.Results:1. Results of univariate logistic regression analysis showed that diabetes duration, insulin therapy, diabetic nephropathy, diabetes complicated by coronary artery disease, history of hypertension, hypertension control, systolic pressure, family history of diabetes, serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, uric acid, urea nitrogen, creatinine and urine albumin excretion rate were significantly associated with diabetic retinopathy in type 2 diabetic patients. The OR and its 95%CI were as follows: 1.651(1.404-1.942),2.148(1.488-3.102),2.322(1.597-3.374).2.199(1.513-3.1970), 1.487(1.040-2.125),1.513(1.147-1.997),1.257(1.108-1.425),1.560(1.014-2.400), 1.576(1.119-2.217),1.380(1.036-1.838),1.380(1.075-1.772),1.710(1.130-2.588), 1.639(1.060-2.536),1.572(1.074-2.301) and 2.181(1.516-3.138). After adjusting for possible confounding factors, the associations between high-density lipoprotein cholesterol, urea nitrogen and creatinine with diabetic retinopathy were not existed. No associations were found between diabetic retinopathy with age, gender, education, occupational type, marital status, hemoglobin Alc, fasting blood glucose, postprandial 2 hours blood glucose, ketosis, diabetic peripheral neuropathy, diabetic foot, family history of hypertension, family history of coronary artery disease, hyperlipidemia, smoking, drinking, regular exercise, character, tramuma, diastolic pressure, triglycerides, very low-density lipoprotein cholesterol, body mass index and waist-to-hip ratio.2. The genotype frequencies of MTHFR gene in case group were 16.15%,48.45% and 35.40% and 36.15%,44.60% and 19.25% in control group for CC, CT and TT genotypes, respectively. The difference of the genotype frequencies of the MTHFR gene between the two groups was statistical significance (χ2=22.745, P<0.001). The allele frequencies of MTHFR gene were 40.37% and 59.63% in case group and 58.45% and 41.55% in control group for allele C and T, respectively. The difference of the allele frequencies of MTHFR gene between the two groups was statistical significance (χ2=23.977, P<0.001). Results of univariate logistic regression analysis showed that type 2 diabetic patients with MTHFR gene had high risk of diabetic retinopathy, its OR (95%CI) were 2.013(1.497-2.708), and still statistically significant after adjusting for family history of diabetes and AR gene. Type 2 diabetic patients with CT/TT genotype of MTHFR gene had high risk of diabetic retinopathy, its OR (95%CI) were 2.940(1.775-4.868), and still statistically significant after adjusting for family history of diabetes. Type 2 diabetic patients with T allele of MTHFR gene had high risk of diabetic retinopathy, its OR (95%CI) were 2.078(1.548-2.789).3. The genotype frequencies of AR gene in case group were 11.18%,35.40% and 53.42% and 12.21%,47.88% and 39.91% in control group for TT,CT and CC genotypes, respectively. The difference of the genotype frequencies of AR gene between the two groups was statistical significance (χ2=7.104, P=0.029). The allele frequencies of AR gene were 71.12% and 28.88% in case group and 63.85% and 36.15% in control group for allele C and T, respectively. The difference of the allele frequencies of the AR gene between the two groups was statistical significance (χ2=4.380, P=0.036). Results of univariate logistic regression analysis showed that type 2 diabetic patients with AR gene had low risk of diabetic retinopathy, its OR (95%CI) were 0.725(0.533-0.987), and still statistically significant after adjusting for family history of diabetes and MTHFR gene. Type 2 diabetic patients with CT/TT genotype of AR gene had low risk of diabetic retinopathy, its OR (95%CI) were 0.579(0.383-0.876), and still statistically significant after adjusting for family history of diabetes. Type 2 diabetic patients with T allele of AR gene had low risk of diabetic retinopathy, its OR (95%CI) were 0.717(0.525-0.980).4. Main effect model of non-conditional logistic regression was analyzed. Five factors related to diabetic retinopathy were introducted into multivariate non-conditional logistic regression equation, which included diabetes duration, insulin therapy, urine albumin excretion rate, MTHFR CT/TT genetype, AR CT/TT genetype. The ORs (95%Cls) were as follows:1.398 (1.106-1.767),1.748 (1.025-2.979),2.142(1.151-3.986),2.215 (1.563-3.183) and 0.657 (0.453-0.952).Conclusions:Longer diabetes duration, insulin therapy, urine albumin excretion rate, MTHFR CT/TT genetype, AR CC genetype were related to high risk of diabetic retinopathy. |
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