Polymorphisms in Turkish population

Gazi University, Faculty of Medicine.

Hypoxia-inducible factor-1 (HIF-1), an important genetic component of angiogenesis, becomes stable as a response to tumor hypoxia and facilitates tumor survival. The polymorphisms of the HIF-1alpha gene may cause changes in the activity of the protein which serves as a transcription factor for many genes in tumorigenesis. In this study, we have investigated the relationship between seven HIF-1alpha polymorphisms [C>T substitution in intron 8 (rs10873142), T418I (rs41508050) in exon 10, P564P (rs41492849), L580L (rs34005929), P582S (rs11549465), A588T (rs11549467) in exon 12 and dinucleotide GT repeat in intron 13 (rs10645014)] among lung cancer patients in the Turkish population. Genomic DNA was isolated from 141 lung cancer cases and 156 controls and subjected to PCR for amplification. Genotyping was carried out with RFLP and DNA sequencing methods. There was no significant difference between lung cancer cases and controls in terms of the distribution of genotyping frequencies of seven HIF-1alpha polymorphisms (P>0.05). No significant relationship was found between the C>T substitution in intron 8 and P582S haplotypes and development of lung cancer. Also, no significant difference was observed between the genotypes and clinopathological characteristics of the cases. These findings showed that polymorphisms of the HIF-1alpha gene did not confer susceptibility to lung cancer.

Akdeniz University Teknocity, Kampus Antalya, Turkey.

Cytotoxic T lymphocyte-associated antigen-4 is a cell-surface molecule providing a negative signal for T cell activation. CTLA-4 gene polymorphisms are known to be related with genetic susceptibility to various autoimmune diseases, including systemic lupus erythematosus (SLE). However, the effects of this polymorphism on clinical features of SLE have not been defined. We analysed the CTLA-4 gene +49 A/G polymorphisms in patients with SLE by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and investigated the effect of polymorphisms on clinical outcomes. Blood was collected from 47 unrelated Turkish SLE patients, all fulfilling the American College of Rheumatology criteria for SLE, and 100 ethnically matched healthy volunteers. The AA genotype was a predominant genotype in the Turkish population and genotype frequencies of CTLA-4 AA were significantly higher in SLE patients (70%) than healthy controls (47%) (P = 0.015). There was a statistically significant difference in the AA genotype [odds ratio (OR): 2.66, confidence interval (CI) 95%: 1.27-5.56, P = 0.014] distribution among patients and controls. There was also an increase in A allele frequency in SLE and controls, but the difference was not statistically significant (81% vs. 70%, P = 0.068, OR = 1.8, CI 95%: 0.99-3.28). Interestingly, mean age and mean age of onset disease was higher in AA homozygote SLE patients compared to non-AA (39.2 +/- 11.5 vs. 31.6 +/- 10.6, P = 0.044; 32.38 vs. 24.31, P = 0.046, respectively). There was no association between genotype and the other clinical features of SLE. Our results suggested that CTLA-4 +49 AA genotype might be a risk factor for the development of SLE in Turkish population and G allele might be involved in early development of SLE. No association with clinical features was found for polymorphism of the promoter region in CTLA-4 +49.