Association of Vitamin D Receptor Polymorphisms to Pulmonary Tuberculosis in Turkish Patients: An Up-to-date Meta-Analysis and A Case-Control Study

Abstract
Introduction: Tuberculosis is a major global health issue, threatening millions of lives every year. To understand the interactions between host and the pathogenic factors, many association studies are being held in different populations and most of the time results are controversial. Vitamin D receptor is one of the immunomodulatory molecules that may have an effect on susceptibility to tuber-culosis. Up to now, there was no positive association reported with the tuberculosis and Fok I or Taq I polymorphisms of VDR gene in tuberculosis patients of Turkish origin. The aim of this study was to make an updated meta-analysis and a case-control study in our group of patients for figuring out the association between Fok I and Taq I polymorphisms of VDR and TB. Materials and Methods: In the present study, association of pulmonary tuberculosis and VDR gene's Fok I (rs 2228570) and Taq I (rs20731236) polymorphisms were investigated in our patient group from Malatya, and a comparison was made by a meta-analysis with the mentioned polymorphisms. Ninety-four healthy controls and 80 patients are subjects of case control study. The samples are genotyped for Taq I and Fok I polymorphisms by using TaqMan SNP genotyping kits. The allelic and genotypic distributions were analyzed by exact significance of the Pearson's test or Fisher's exact tests. Meta-analyses for each SNP were conducted under four different genetic models. The statistical significance of the pooled ORs was determined by a Z test and publication bias was evaluated by Egger's test. Results: Our case control study Taq I polymorphism showed no significant association to TB which also matched with our meta-analysis. On the other hand, for Fok I polymorphism, genotypes and allele frequencies were significantly different in our focus group (p 0.044). Sex based analysis gave significantly different results in women with TB as well even though our meta-analysis showed no association to that polymorphism. Conclusion: The reasons underlying the susceptibility to TB is still not clear. The immune response process is so complex and many molecules are taking part in these reactions. So, there are a lot of candidate molecules to be checked in the association studies. VDR is still one of those molecules and may be other than by checking single SNPs, haplotypes could be under investigation with bigger populations.