Angiotensin-converting enzyme gene polymorphisms and T2DM in a case–control association study of the Bahraini population

Al-Jawhara Centre for Molecular Medicine, Genetics and Inherited Disorders, Arabian Gulf University, Manama, Kingdom of Bahrain.
Molecular and Cellular Biochemistry (Impact Factor: 2.39). 04/2011; 350(1-2):119-25. DOI: 10.1007/s11010-010-0688-y
Source: PubMed


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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Available from: Einas M Al-Harbi, May 19, 2015
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    • "Genetic markers, in particular ACE I/D gene polymorphism, might offer some benefits to better predict the outcome of renal diseases. The level of plasma ACE, constitutively expressed in several types of somatic cells, is linked to an I/D gene polymorphism of 287 bp in intron 16 of the ACE gene [7, 12]. The D allele and DD genotype has been reported to be associated with higher plasma ACE level [13]. "
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    ABSTRACT: Aim. This meta-analysis was performed to evaluate the association between ACE I/D gene polymorphism and MCNS susceptibility. Method. A predefined literature search and selection of eligible relevant studies were performed to collect the data from electronic databases. Results. Six articles were identified for the analysis of association between ACE I/D gene polymorphism and MCNS risk, including 4 for Asians, one in Caucasian population and one for Africans. There was a markedly positive association between D allele or DD genotype and MCNS susceptibility in Asians (D: P = .01, DD: P = .02), but not for Caucasians and Africans (Caucasians: D: P = .16, DD: P = .98; Africans: D: P = .81, DD: P = .49). Furthermore, the II genotype seemed not to play a protective role against MCNS risk for Asians, Caucasians and Africans (P = .12, P = .09, P = .76, resp.). Interestingly, there was also significant association between ACE I/D gene polymorphism and MCNS susceptibility in overall populations (D: P = .007, DD: P = .04, II: P = .03). Conclusion. D allele or DD genotype might be a significant genetic molecular marker for MCNS susceptibility in Asians and overall populations, but not for Caucasians and Africans. More larger and rigorous genetic epidemiological investigations are required to further explore this association.
    05/2011; 2011:360357. DOI:10.4061/2011/360357
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    The British Journal of Diabetes & Vascular Disease 01/2011; 11:153-154. DOI:10.1177/1474651411412662
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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. DOI:10.1007/s11010-011-1017-9 · 2.39 Impact Factor
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