Association of HLA class II alleles and CTLA-4 polymorphism with type 1 diabetes.

Type-1 diabetes mellitus (T1DM) is a progressive complex autoimmune disease in which combinations of environmental as well as genetic factors contribute to T-cell mediated destruction of insulin-secreting ß-cells of the pancreas. HLA class II alleles on chromosome 6p21 [insulin dependent diabetes mellitus 1 (IDDM1)], especially DR and DQ, show strong association with T1DM. In addition, several studies have suggested that polymorphisms in the CTLA-4 gene (IDDM12) on chromosome 2q33 form part of the genetic susceptibility for type 1 diabetes. The aim of this study was to analyze HLA alleles of the DQB1 and DRB1 genes using polymerase chain reaction using sequence specific primers (PCR-SSP) technique and to investigate the association of the A49G CTLA-4 polymorphism using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in Lebanese T1DM patients. The study was conducted on 39 Lebanese T1DM patients. Results of HLA typing showed an increased frequency of the HLA-DQB1FNx010201, HLA-DQB1FNx010302, HLA-DRB1FNx010301 and HLA-DRB1FNx010401 alleles, suggesting risk association and thus can be considered as susceptibility alleles. On the other hand, strong protection against the disease was conferred by the HLA-DRB1FNx01110101, HLA-DQB1FNx010301 and HLADQB1FNx010601 alleles. RFLP analysis of the A49G polymorphism showed a significant increase in the G allele and GG genotype frequencies in patients, suggesting that CTLA-4 may be considered as a susceptibility gene for the development of T1DM in the Lebanese population. Analysis of the two polymorphisms showed no detectable association between the two genes. However, a significant negative association of the G allele with the DQB1FNx010201 allele was observed. This might indicate that the two genetic risk factors, namely HLA and CTLA-4, act independently of each other with no additive effect.

Association between angiotensin-converting enzyme insertion/deletion genetic polymorphism and hypertension in a sample of Lebanese patients.

BACKGROUND/AIM: several studies have looked at the potential link between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and the risk of hypertension and have shown that the DD polymorphism may be associated with a higher prevalence of hypertension. Our objective was to assess for possible association between ACE variants and hypertension in a sample of Lebanese patients. METHODS: one hundred ninety-two Lebanese subjects were included. DNA was isolated and amplified by polymerase chain reaction. The products were identified by gel electrophoresis according to their size. RESULTS: one hundred fifteen (59.9%) patients were hypertensive and 77 (40.1%) were nonhypertensive with the following genotype frequencies: 43.4% DD, 45.2% ID, and 11.4% II compared with 35.2% DD, 51.9% ID, and 12.9% II, respectively. Age was found to be the most significant risk factor for hypertension. This was more prominent when accounting for ACE genotype; for instance, the DD genotype with age had a significantly higher odds ratio (OR = 11.852; p = 0.001) than the ID genotype with age (OR = 4.599; p = 0.006), II genotype with age (OR = 1.866; p = 0.519), and age alone (OR = 5.558; p = 0.006). CONCLUSION: our results show that the ACE I/D polymorphism is common in Lebanon, and the combinations of ACE D allele and age is associated with an increased risk of hypertension.

A study on the association between angiotensin-I converting enzyme I/D dimorphism and type-2 diabetes mellitus.

Type-2 diabetes mellitus (T2DM) is a chronic disorder characterized by a varying range of predominant insulin resistance with relative insulin deficiency, to predominant insulin secretory defect with or without insulin resistance. Familial clustering as well as epidemiological studies has shown that genetic factors play a role in the development and progression of the disease. Among the genetic factors found to be associated with development of T2DM is the angiotensin-I converting enzyme (ACE) gene, which is located on chromosome 17q23. This study was conducted to study the association between ACE gene insertion/deletion (I/D) polymorphism and T2DM in a Lebanese diabetic cohort. Fifty-one patients with T2DM and 40 control subjects from different parts of Lebanon underwent genotyping for the ACE I/D, which was performed by PCR using specific primers. Chi-square and analysis of variance (ANOVA) were used for association studies and to assess the differences in the values among the groups. The distribution of the genotypes in the patients was as follows: 15/51 (29.4%) were homozygous for deletion allele (DD genotype), 24/51 (47.1%) were heterozygous (ID genotype), and 12/51 (23.5%) were homozygous for insertion allele (II genotype). Among the control subjects, 16/40 (40%) were homozygous for deletion (DD genotype), 13/40 (32.5%) were heterozygous (ID genotype), and 11/40 (27.5%) were homozygous for insertion (II genotype). The prevalence of the D-allele in T2DM patients (52.9%) was not significantly different from that in the controls (56.3%). Thus, ACE I/D dimorphism cannot be considered a risk factor for T2DM in the Lebanese population.