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New variant identified in major susceptibility locus to tuberculosis on chromosomal region 8q12-q13 in Moroccan population: a case control study.在摩洛哥人群中位于染色体8q12 - q13区域的结核病主要易感基因座中鉴定出的新变体：一项病例对照研究。
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本文引用的文献

1
Age-dependent association between pulmonary tuberculosis and common TOX variants in the 8q12-13 linkage region.年龄相关的肺结核与 8q12-13 连锁区域常见 TOX 变异体的关联。
Am J Hum Genet. 2013 Mar 7;92(3):407-14. doi: 10.1016/j.ajhg.2013.01.013. Epub 2013 Feb 14.
2
The MCP-1 (CCL2) -2518 GG genotype is associated with protection against pulmonary tuberculosis in Moroccan patients.MCP-1（CCL2）-2518 GG基因型与摩洛哥患者肺结核的防护相关。
J Infect Dev Ctries. 2012 Jan 12;6(1):73-8. doi: 10.3855/jidc.1925.
3
Cholesterol catabolism as a therapeutic target in Mycobacterium tuberculosis.胆固醇分解代谢作为结核分枝杆菌的治疗靶点。
Trends Microbiol. 2011 Nov;19(11):530-9. doi: 10.1016/j.tim.2011.07.009. Epub 2011 Sep 15.
4
Formation and aggregation of lipid rafts in γδ T cells following stimulation with Mycobacterium tuberculosis antigens.刺激分枝杆菌抗原后，γδ T 细胞中脂筏的形成和聚集。
Tohoku J Exp Med. 2011 Mar;223(3):193-8. doi: 10.1620/tjem.223.193.
5
CYP7A1 genotypes and haplotypes associated with hypertension in an obese Han Chinese population.与肥胖汉族人群高血压相关的 CYP7A1 基因型和单倍型。
Hypertens Res. 2011 Jun;34(6):722-7. doi: 10.1038/hr.2011.18. Epub 2011 Feb 24.
6
Promoter variant -204A > C of the cholesterol 7α-hydroxylase gene: association with response to plant sterols in humans and increased transcriptional activity in transfected HepG2 cells.胆固醇 7α-羟化酶基因启动子变异 -204A > C：与人体对植物固醇的反应相关，并增加转染 HepG2 细胞的转录活性。
Clin Nutr. 2011 Apr;30(2):239-46. doi: 10.1016/j.clnu.2010.07.020. Epub 2010 Sep 29.
7
Caseation of human tuberculosis granulomas correlates with elevated host lipid metabolism.人类结核肉芽肿的干酪样坏死与宿主脂质代谢升高相关。
EMBO Mol Med. 2010 Jul;2(7):258-74. doi: 10.1002/emmm.201000079.
8
Mycobacterium tuberculosis CYP125A1, a steroid C27 monooxygenase that detoxifies intracellularly generated cholest-4-en-3-one.结核分枝杆菌 CYP125A1，一种甾体 C27 单加氧酶，可解毒细胞内产生的胆甾-4-烯-3-酮。
Mol Microbiol. 2010 Aug;77(3):730-42. doi: 10.1111/j.1365-2958.2010.07243.x. Epub 2010 Jun 10.
9
Analysis of MIF, FCGR2A and FCGR3A gene polymorphisms with susceptibility to pulmonary tuberculosis in Moroccan population.分析摩洛哥人群中 MIF、FCGR2A 和 FCGR3A 基因多态性与肺结核易感性的关系。
J Genet Genomics. 2010 Apr;37(4):257-64. doi: 10.1016/S1673-8527(09)60044-8.
10
Genetic susceptibility in tuberculosis.结核病的遗传易感性。
Respirology. 2010 Feb;15(2):241-56. doi: 10.1111/j.1440-1843.2009.01690.x.

CYP7A1基因rs3808607变异与摩洛哥人群的结核病易感性相关。

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

作者信息

Qrafli Mounia, Amar Youssef, Bourkadi Jamaleddine, Ben Amor Jouda, Iraki Ghali, Bakri Youssef, Amzazi Saaîd, Lahlou Ouafae, Seghrouchni Fouad, El Aouad Rajae, Sadki Khalid

机构信息

Laboratory of Human Genomic, National Institute of Hygiene, Rabat, Morocco ; Laboratory of Biochemistry and Immunology, Faculty of Sciences, University Mohammed V, Rabat, Morocco.

Laboratory of Biochemistry and Immunology, Faculty of Sciences, University Mohammed V, Rabat, Morocco.

出版信息

Pan Afr Med J. 2014 May 1;18:1. doi: 10.11604/pamj.2014.18.1.3397. eCollection 2014.

DOI:10.11604/pamj.2014.18.1.3397
PMID:25360185
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4212432/
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.

摘要

引言

尽管在治疗方面取得了医学进展，但结核病（TB）仍然是一个严重的全球健康问题。一项全基因组连锁研究在摩洛哥结核病患者中确定了染色体区域8q12 - q13上的一个主要易感基因座。CYP7A1基因位于该区域，编码胆固醇7α - 羟化酶，这是一种参与胆固醇分解代谢的酶。

方法

我们选择了三个单核苷酸多态性（SNP，rs3808607、rs8192875和rs8192879），研究它们在肺结核（PTB）或结核性胸膜炎（pTB）患者中的基因型和等位基因频率分布，并将其与健康对照（HC）进行比较。使用Taq Man SNP基因分型检测法对rs8192875和rs8192879 SNP进行基因分型，而rs3808607则通过PCR - RFLP进行研究。

结果

我们首次报告，与HC相比，PTB患者中rs3808607的AA纯合子基因型频率有统计学意义的增加（p = 0.02，OR = 1.93，95% CI：1.93（1.07；3.49）。当我们合并患者组（PTB - pTB）时，患结核病风险增加的情况依然存在（p = 0.01，OR = 1.91，95% CI =（1.07 - 3.42）。相比之下，未观察到rs8192875或rs8192879多态性与结核病之间存在遗传关联。

结论

我们的数据表明rs3808607可能在摩洛哥人群对结核病的易感性中起作用。