Angiotensin-converting enzyme gene polymorphisms and T2DM in a case-control association study of the Bahraini population.
ABSTRACT Bahrain has one of the highest incidence rates of type 2 diabetes mellitus (T2DM). Development of diabetic nephropathy (DN) as a complication was noticed in some patients while absent in others. This interesting observation raises the role of certain genetic risk factors for the development of DN. Angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism was found to be associated with T2DM. While some patients have predisposition to DN in the population, others have negative association. The present case-control association study was designed to investigate the association of ACE I/D polymorphism in T2DM patients in Bahrain especially in those who developed DN. A total of 360 T2DM patients (110 with DN and 250 without DN) and 360 healthy (non-diabetic) age-matched subjects were recruited for this study for comparison. The presence (insertion)/absence (deletion) (I/D) polymorphism of a 287-bp Alu1 element inside intron 16 of the ACE gene was investigated using PCR-gel electrophoresis. The results show that the distribution of the homozygote DD genotype of the ACE gene was high among Bahraini T2DM patients compared to the healthy non-diabetic subjects. In addition, the distribution of the deletion (D) allele was high among Bahraini T2DM patients with DN when compared to the healthy non-diabetic subjects. However, there was no significant difference in the distribution of ACE I/D allele and genotypes between DN patients when compared to those T2DM patients without DN. The results obtained in this study are in closely agreement with some previous reports which show a strong association of ACE polymorphism with T2DM patients, yet not a risk factor for development of DN.
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ABSTRACT: The PvuII and XbaI polymorphisms of the estrogen receptor α (ER1) gene have been variably associated with type 2 diabetes (T2D) in several populations. However, this association has not been studied in Iranian subjects and we hypothesized that the ER1 variants might be associated with T2D and related metabolic traits in this population. The PvuII and XbaI genotypes were determined by PCR-RFLP in 377 normoglycemic controls and 155 T2D patients. Bonferroni correction was applied for the correction of multiple testing. No significant association was found between the allele and genotype frequencies of PvuII and XbaI variants with T2D in females. In a dominant model (PP vs. Pp+pp), the frequency of the Pp+pp genotype was higher in normoglycemic subjects compared to T2D patients [85.5% vs. 66.7%, OR 0.22 (0.08-0.55), P=0.001]. Four possible haplotypes were observed in the population, whereas haplotype TA had a higher frequency in male T2D subjects than the controls. Furthermore, non-diabetic male subjects carrying the genotype of PP had a higher fasting glucose levels than the individuals with the genotype of Pp+pp (P=0.013). Multivariate logistic regression analysis showed that PvuII polymorphism was the independent determinants of T2D in males [OR 4.37 (1.61-11.86), P=0.004]. No association was found between the XbaI polymorphism and diabetes in male group. Our results suggest that the ER1 polymorphisms might associate with T2D and fasting glucose among Iranian male subjects.Molecular and Cellular Biochemistry 08/2011; 359(1-2):225-33. · 2.33 Impact Factor
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ABSTRACT: Background. One of the most common complications of diabetes mellitus (DM) is diabetic nephropathy (DN). Angiotensin- converting enzyme (ACE) gene was the first candidate gene of renin-angiotensin system (RAS) for predisposition to DN. Objective. Investigation whether the ACE insertion/deletion (I/D) polymorphism is associated with Egyptian type 2 diabetic patients (T2DM) with nephropathy. In addition, the study investigated the relationship between variants of ACE I/D gene polymorphism and serum ACE level and the progression of nephropathy in Egyptian T2DM patients. Methods. A total of 85 T2DM patients (45 with nephropathy and 40 without nephropathy) besides 45 healthy (non-diabetic) age-matched subjects were recruited in this study for comparison. The (I/D) polymorphism of the ACE gene was investigated using PCR and serum ACE levels were determined using ELISA. Results. The frequency of ACE DD genotype and D allele was significantly higher in DN patients when compared to control healthy subjects and diabetic patients without nephropathy. In addition our results showed a significant association between DD genotype of ACE gene and elevated serum ACE level. Conclusion. The present study showing a strong association between the D allele and/or DD homozygous of ACE gene and diabetic patients developed nephropathy. In addition, individuals with D allele have higher levels of serum ACE compared to those having I allele. ACE gene polymorphism and serum ACE level may serve as a susceptibility biomarker for nephropathy in type 2 diabetic patients.Journal of Advances in Chemistry. 05/2014; 9(3):2023-2032.
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ABSTRACT: Associations between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphisms and chronic kidney disease (CKD) have been extensively studied, with most studies reporting that individuals with the D allele have a higher risk. Although some factors, such as ethnicity, may moderate the association between ACE I/D polymorphisms and CKD risk, gender-dependent effects on the CKD risk remain controversial. This study investigated the gender-dependent effects of ACE I/D polymorphisms on CKD risk. PubMed, the Cochrane library, and EMBASE were searched for studies published before January 2013. Cross-sectional surveys and case-control studies analyzing ACE I/D polymorphisms and CKD were included. They were required to match the following criteria: age >18 years, absence of rare diseases, and Asian or Caucasian ethnicity. The effect of carrying the D allele on CKD risk was assessed by meta-analysis and meta-regression using random-effects models. ETHNICITY [ODDS RATIO (OR): 1.24; 95% confidence interval (CI): 1.08-1.42] and hypertension (OR: 1.55; 95% CI: 1.04-2.32) had significant moderate effects on the association between ACE I/D polymorphisms and CKD risk, but they were not significant in the diabetic nephropathy subgroup. Males had higher OR for the association between ACE I/D polymorphisms and CKD risk than females in Asians but not Caucasians, regardless of adjustment for hypertension (p<0.05). In subgroup analyses, this result was significant in the nondiabetic nephropathy group. Compared with the I allele, the D allele had the highest risk (OR: 3.75; 95% CI: 1.84-7.65) for CKD in hypertensive Asian males. The ACE I/D polymorphisms may incur the highest risk for increasing CKD in hypertensive Asian males.PLoS ONE 01/2014; 9(1):e87604. · 3.73 Impact Factor