Association analysis of cholesterol 7-alpha hydroxylase (CYP7A1)and cholesterol 24-hydroxlase (CYP46A1) genetic polymorphisms and multiple sclerosis risk in Turkish population

Sezer, Eda
Multiple Sclerosis (MS) is the most common demyelinating disorder of the central nervous system. Under the effects of certain environmental factors, MS develops in genetically susceptible individuals. People with MS have significantly lower vitamin D levels. UV-B radiation catalyzes the photo-conversion of 7-dehydrocholesterol, produced in cholesterol production pathway, to vitamin D in the skin. Cholesterol 7α-hydroxylase (CYP7A1) in the liver and Cholesterol 24S-hydroxylase (CYP46A1) in the brain are responsible for cholesterol removal in human body. A Single Nucleotide Polymorphism (SNP) conferring A→C transition, named rs3808607 in CYP7A1 and present at -204 location of form the transcriptional start site, might play a critical role in gene expression and its enzyme activity. T → C SNP named rs754203 in CYP46A1, which is located in intronic region of CYP46 gene, 151 bases 5′ to exon 3, is investigated in terms of human health or disease although it does not affect the amino acids sequences or the structure of the protein expressed by gene. In this study, rs3808607 and rs754203 polymorphisms were investigated for their effect on the risk of MS. 138 MS patients and 100 healthy controls were tested by PCR-RFLP method to determine their genotypes. Analyses of them were conducted by forming three genetic models of SNPs: Dominant, Recessive and Additive Model. For CYP7A1 rs3808607 and CYP46A1 rs754203, all genotypes and allele frequency analyses were performed with all subjects, male and female subgroups only. However, any significant difference was not found in them. To understand whether there were any relations of blood lipids and vitamin D levels in MS patients and controls with rs3808607 and rs754203, SNPs were split according to mentioned genetic models. For rs3808607, only its recessive model, TC and vitamin D contents of patients, carrying the wild type allele were significantly lower than controls with same genotypes. The other comparisons didn’t show any meaningful difference. As regard to CYP46A1 rs754203 SNP, of all the comparisons, only statistical significance was that vitamin D levels of patients with heterozygote mutant genotype was lower than controls with same genotype. As a conclusion, in this study, there were no any significant associations between genotypes and allele frequencies of CYP7A1 rs3808607 and CYP46A1 rs754203 SNPs and MS risk. In terms of lipid parameters and vitamin D levels, these genes and lipid parameters were not found to be related in patients and controls, however, vitamin D levels were found to be lower in patients compared to controls in some subgroups.


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Citation Formats
E. Sezer, “Association analysis of cholesterol 7-alpha hydroxylase (CYP7A1)and cholesterol 24-hydroxlase (CYP46A1) genetic polymorphisms and multiple sclerosis risk in Turkish population,” Thesis (M.S.) -- Graduate School of Natural and Applied Sciences. Molecular Biology and Genetics, Middle East Technical University, 2019.