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

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.

The MCP-1 (CCL2) -2518 GG genotype is associated with protection against pulmonary tuberculosis in Moroccan patients.

INTRODUCTION: Both monocyte chemoattractant protein-1 (MCP-1), also designated officially as chemokine (C-C motif) ligand 2 (CCL2), and interleukin-12 p40 (IL-12 p40) molecules, encoded by polymorphic genes, are central components of the immune response to infection by Mycobacterium tuberculosis (Mtb). Their genetic diversity has previously been associated with the outcome of tuberculosis (TB) infection. We investigated whether the MCP-1 -2518 A/G and the IL-12B (p40) +1188 A/C polymorphisms influence susceptibility to or resistance against pulmonary tuberculosis (PTB) in a Moroccan population group. METHODOLOGY: Genomic DNA from 337 patients along with 204 healthy controls were genotyped for the above-mentioned genetic variations using polymerase chain reaction-based restriction fragment length polymorphism assay. RESULTS: We found a higher prevalence of homozygous MCP-1 -2518 G allele in healthy individuals than in patients (pc = 0.04; odds ratio  = 0.35; 95% confidence interval  = 0.13 - 0.86), suggesting a potential protective effect, whereas analysis of IL-12B +1188 variation failed to reveal any such association. CONCLUSION: Our results are in agreement with recent findings in Ghanaian patients, complying with the known genetic admixture of the Moroccan population.