| Objectives: The aim of this study was to explore the associations between insertion/deletion (I/D) polymorphism of Alu sequence at intron 16 of the polymorphism of angiotensin-converting enzyme (ACE) gene and other factors and diabetic nephropathy(DN) in type 2 diabetic patients.Methods: A hospital-based case-control study was conducted in Tianjin from November 2001 to January 2003. 101 pairs of subjects were recruited. The cases were considered to be DN patients and the controls were considered to be type 2 diabetic patients (DM) without diabetic nephropathy. Each case was matched with one control on sex and age. Information was collected through face-to-face interview, which included demographic data, disease history, disease family history, dietetic habit, behavior pattern, social psychologic character, clinical data and laboratory data. I/D polymorphism of ACE gene was assessed by polymerase chain reaction (PCR) and the PCR products were subjected to electrophoresis on agarose gel that was stained with ethidium bromide. Using the conditional logistic regression model, we examined the effect of the collected factors on the risk of the diabetic nephropathy development. Results: Results from univariate conditional logistic regression analysis showedthat the I/D polymorphism of ACE gene was associated with development of diabetic nephropathy. D allele was more frequency among DN patients. Compared with the group of II genotype, the corresponding OR with 95% CI of the groups of ID genotype and DD genotype were 2.419( 1.180~4.959)and 3.417 (1.608~7.260) respectively. After adjusting for diabetic family history and history of hypertension, the results still showed that the association between ACE genotype and DN was statistically significant. Results from univariate conditional logistic regression analysis also showed that DN was associated with education level, diabetes duration, glycemia control, diabetic family history, history of hypertension, hypertension treatment, legume intake, serum creatinine level and serum level of high density lipoprotein (HDL) cholesterol. The corresponding OR with 95% CI were 0.400(0.176-0.908), 1.907(1.399-2.601), 1.553(1.033-2.337), 2.000(1.097-3.644), 2.055(1.170-3.610), 1.540(1.123-2.111), 1.359 (1.010-1.828), 4.000(1.927-8.304) and 0.390(0.164-0.924) respectively. However, after adjusting for possible confounding factors, the associations between these factors, including education level, glycemia control, hypertension treatment and serum HDL cholesterol level, and DN were statistically significant. No associations were observed between the following factors and DN, which were family history of hypertension, family history of coronary heart disease, exercise, smoking, alcohol drinking, tea drinking, meat intake, egg intake, milk intake, fat intake, vegetable intake, sweetmeat intake, times of pregnancy, the history of delivering macrosomia, character, body index, serum total cholesterol, triglycerides, low density lipoprotein and very low density lipoprotein cholesterol levels. ACE genotype and diabetes duration were found to have an interaction(OR=1.741, 95%CI:1.107 -2.740). When subjected to multivariate conditional logistic regression analysis, four factors remained statisticalassociations with DN, which were ACE genotype(OR=1.890, 95%CI:1.146~ 3.118), diabetes duration(OR=2.302, 95%CI:1.507 ~ 3.515), legume intake (OR=1.629, 95%CI:1.054~ 2.519) and serum creatinine level (OR=5.918, 95%CI:2.224~ 15.750). No association was observed between I/D polymorphism of ACE gene and DN stage.Conclusion: D allele of ACE gene was an independent predictive factor for diabetic nephropathy, long diabetes duration, increased legume intake and high serum creatinine level were associated with higher risk for the development of diabetic nephropathy.
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