The CYP7A1 gene rs3808607 variant is associated with susceptibility of tuberculosis in Moroccan population

Abstract

Introduction: Despite the medical progress in treatment. Tuberculosis (TB) continues to be a serious global health problem. A genome-wide linkage study identified a major susceptibility locus on  chromosomal region 8q12-q13 in Moroccan TB patients. The CYP7A1 gene is located in this region and codes for cholesterol 7a-hydroxylase, an enzyme involved in cholesterol catabolism.

Methods: We selected three SNPs (rs3808607, rs8192875 and rs8192879) and studied their genotype and allele frequencies distribution in patients with pulmonary (PTB) or pleural TB (pTB), and compared them to Healthy Controls (HC). Genotyping of rs8192875 and rs8192879 SNPs was carried out using the Taq Man SNP genotyping Assay while rs3808607 was investigated by PCR-RFLP.

Results: We reported here for the first time a statistically significant increase in the AA homozygote genotype frequency of rs3808607 in PTB patients compared to HC (p = 0.02, OR = 1.93, 95% CI: 1.93 (1.07;3.49). The increased risk of developing TB was maintained when we combined the groups of patients (PTB-pTB) (p = 0.01, OR= 1.91, 95% CI = (1.07 - 3.42). In contrast, no genetic association was observed between the rs8192875 or rs8192879 polymorphisms and TB.

Conclusion: Our investigations suggest that rs3808607 may play a role in susceptibility to TB in a Moroccan population.

Key words: Tuberculosis, cholesterol 7-alpha-hydroxylase, polymorphisms, SNPs, cholesterol