Abstract
IntroductionDespite 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.MethodsWe 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.ResultsWe 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.ConclusionOur investigations suggest that rs3808607 may play a role in susceptibility to TB in a Moroccan population.
Highlights
In view of the toxicity associated with the accumulation in Mycobacterium tuberculosis (Mtb) of some cholesterol metabolites such cholest-4-en-3-one [9], it has been suggested that the cholesterol degradation pathway could be an interesting avenue for the development of new anti-tuberculosis agents [10]
We examined the polymorphism of three SNPs located in the CYP7A1 gene and evaluated their impact on susceptibility to TB of a Moroccan population by using a case-control approach
A significant statistical difference in both the AA genotype and A allele frequencies have been observed between PTB patients and Healthy controls (HC) (43% vs 28 %, p = 0.026, odds ratio (OR) = 1.94, 95% confidence interval (CI) = 1.03-3.65 and 65% vs 54%, p = 0.025, OR = 1.58, 95% CI =1.04–2.4, respectively)
Summary
Several studies have demonstrated the important role played by cholesterol in the function of the immune system [6,7]. In view of the toxicity associated with the accumulation in Mtb of some cholesterol metabolites such cholest-4-en-3-one [9], it has been suggested that the cholesterol degradation pathway could be an interesting avenue for the development of new anti-tuberculosis agents [10]. It has been reported that host cholesterol is involved in Mtb infection and persistence [11,12]. Several studies have reported the important role played by LR in the pathogenesis of Mtb infections [13]. The CYP7A1 gene codes for cholesterol 7alpha-hydroxylase (CYP7A1), a cytochrome P450 that plays an essential role in maintaining a balance in cholesterol and bile acid since its catalytic reaction is the rate-limiting step and the major step in regulating homeostasis of cholesterol and bile acids [14]. The CYP7A1 gene spans about 10 kb and contains 6 exons, 5 introns, one 5 ́-UTR, and one 3 ́-UTR and is localized on chromosome 8q12.1
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