Association of TNF-α Gene Variants With Clinical Manifestation of Cystic Fibrosis Patients of Iranian Azeri Turkish Ethnicity

Background: Cystic fibrosis (CF), a life-limiting autosomal recessive disorder, is considered a monogenic disease that is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. According to several studies, mutation analysis of the cystic fibrosis transmembrane conductance regulator (CFTR) gene alone is insufficient to predict the phenotypic manifestations observed in cystic fibrosis (CF) patients. In addition, some patients with a milder CF phenotype do not carry any pathogenic mutation. Tumor Necrosis Factor-alpha (TNF-α) contributes to the pathophysiology of CF by causing cachexia. There is a reverse association between TNF-α concentration in patient's sputum and their pulmonary function. Objectives: To assess the effect of non-CFTR genes on the clinical phenotype of CF, two polymorphic sites (-1031T/C and -308G/A) of the TNF-α gene, as a modifier, were studied. Patients and Methods: Focusing on the lung and gastrointestinal involvement as well as the poor growth, we first investigated the role of TNF-α gene in the clinical manifestation of CF. Furthermore, based on the hypothesis that the cumulative effect of specific alleles of multiple CF modifier genes, such as TNF-α, may create the final phenotype, we also investigated the potential role of TNF-α in non-classic CF patients without a known pathogenic mutation. In all, 80 CF patients and 157 healthy control subjects of Azeri Turkish ethnicity were studied by the PCR–RFLP method. The chi-square test with Yates' correction and Fisher's exact test were used for statistical analysis. Results: The allele and genotype distribution of the investigated polymorphisms, and their associated haplotypes were similar in all groups. Conclusions: There was no evidence that supported the association of TNF-α gene polymorphisms with non-classic CF disease or the clinical presentation of classic CF.

Association of vitamin D receptor gene variants with polycystic ovary syndrome: A case control study

Background: Vitamin D and insulin play an important role in susceptibility to polycystic ovary syndrome (PCOS), and therefore vitamin D receptor (VDR), parathyroid hormone (PTH), and insulin receptor (INSR) gene variants might be involved in the pathogenesis of PCOS. Objective: The present study was designed to investigate the possible associations between polymorphisms in VDR, PTH, and INSR genes and the risk of PCOS. Materials and Methods: VDR, PTH, and INSR gene variants were genotyped in 35 women with PCOS and 35 controls using Polymerase chain reaction – Restriction fragment length polymorphism method. Furthermore, serum levels of glucose and insulin were measured in all participants. Results: No significant differences were observed for the VDR FokI, VDR Tru9I, VDR TaqI,, PTH DraII, INSR NsiI, and INSR PmlI gene polymorphisms between the women with PCOS and controls. However, after adjustment for confounding factors, the VDR BsmI “Bb” genotype and the VDR ApaI "Aa" genotype were significantly under transmitted to the patients (p= 0.016; OR= 0.250; 95% CI= 0.081-0.769, and p= 0.017; OR= 0.260; 95% CI= 0.086-0.788, respectively). Furthermore, in the women with PCOS, insulin levels were lower in the participants with the INSR NsiI "NN" genotype compared with those with the "Nn + nn" genotypes (P= 0.045). Conclusion: The results showed an association between the VDR gene BsmI and ApaI polymorphisms and PCOS risk. These data also indicated that the INSR "NN" genotype was a marker of decreased insulin in women with PCOS. Our findings, however, do not lend support to the hypothesis that PTH gene DraII variant plays a role in susceptibility to PCOS.