Date

2023-1-25

Author

Bulut, Giray

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Multiple Sclerosis (MS) is the most common nontraumatic cause of young disability. There are many studies indicating the relationship between MS and vitamin D. Activation of vitamin D requires a series of hydroxylations that are conducted by cytochrome P450 enzymes (CYPs). Vitamin D shows its effects by binding to vitamin D receptor (VDR). In the present study, vitamin D metabolism related mitochondrial CYPs (CYP27A1, CYP27B1 and CYP24A1) and VDR gene polymorphisms were selected for investigation. 187 (130 female/57 male) MS patients and 140 (78 female/62 male) control subjects were involved in the study. DNA samples extracted from the blood of MS patients and control subjects were genotyped using RFLP. Three genetic models applied which were additive (wild type homozygous genotype vs heterozygous genotype and wild type genotype vs homozygous mutant genotype), dominant (wild type homozygous vs heterozygous+homozygous mutant) and recessive (wild type homozygous+heterozygous vs homozygous mutant). Also, allele frequencies (wild type vs mutant) were analyzed. All analyzes were applied to male and female subgroups of the samples. Analyzes were done with chi-square method and frequencies of genotypes and alleles compared in between MS patients and the healthy control subjects. In TaqI (rs731236), “A” was the wild type and “G” was the mutant allele. In dominant model analysis result is borderline significant (p=0.051) suggesting that “G” allele reduces the risk (OR:0.642). None of the remaining models’ and subgroups’ analyzes were statistically significant. In CYP24A1 (rs1570669), “A” was the wild type and “G” was mutant allele. In statistical analyzes, AA vs AG additive model (p<0.001, OR:5.413) and dominant model (p<0.001, OR:4.429) results were significant and found to increase the susceptibility to the disease. For female subgroup, AA vs AG additive model (p<0.001, OR:6.693) and dominant model (p<0.001, OR:4.685) and for male subgroup, AA vs AG additive model (p<0.001, OR:4.387) and dominant model (p <0.001, OR:4.277) results were significant and found also to increase susceptibility to the disease. For female subgroup, recessive model result was also statistically significant (p=0.041, OR:0.957). Recessive model analyzes were not significant for general population and the male subgroup. AA vs GG additive model and allele frequency comparisons were not significant for general population and subgroups. For VDR-ApaI (rs7975232), CYP27A1 (rs6709815), and CYP27B1 (rs4646536), none of the analyzes (additive, dominant, recessive models and allele frequency comparisons) were statistically significant (p>0.05) suggesting that there is no correlation between MS and the selected polymorphisms. However, for rs4646536, the population frequency of rare variant (“C” allele) was studied for the first time, and the frequency for patients was 2.41%, for control subjects was 3.31% and for total was 2.95%. By this study association of several polymorphisms (rs7975232, rs6709815, rs4646536) with MS risk were investigated for the first time in Turkish population. We hope our results contribute to understanding of genetic background of MS onset.

Subject Keywords

Vitamin D, Multiple sclerosis, Vitamin D metabolizing CYPs, VDR, gene polymorphism

URI

https://hdl.handle.net/11511/102101

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Graduate School of Natural and Applied Sciences, Thesis