Influence of TLR-8 Gene Polymorphisms (rs3764880 and rs3788935) Associated to Pulmonary Tuberculosis in Kupang, Indonesia

A. Charles, Simeon Penggoam, A. Maskoen, E. Sahiratmadja
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Abstract

Toll-like receptor 8 (TLR-8) is known as part of intracellular signaling transduction for bacterial phagocytosis. Mycobacterium tuberculosis (Mtb) is intracellular pathogenic bacteria that is recognized by this receptor, and genetic variation of TLR-8 might alter susceptibility of the host towards pulmonary tuberculosis (PTB). This study aimed to determine whether TLR-8 gene polymorphisms were associated to PTB in Kupang, Indonesia. This case-control study compared demographic and clinical data between 115 PTB patients and 115 controls, then two TLR-8 single nucleotide polymorphisms (rs3764880 and rs3788935) were explored using the GoldenGate® Genotyping for VeraCode® / BeadXpress Illumina®. There is no significant difference between sex distribution of patient vs control groups. The polymorphisms (rs3764880 and rs3788935) are in Hardy-Weinberg Equilibrium in this population (p > 0.05). The distribution of major vs minor genotypes and alleles of TLR-8 polymorphisms in PTB patients were as followed: rs3764880 (GG vs GA vs AA, 50.0% vs 21.4% vs 28.6% ; G vs A, 60.9% vs 39.1% ) and rs3788935 (GG vs GA vs AA, 53.0% vs 21.7% vs 25.3%; G vs A, 62.9% vs 37.1%). Neither genotypes nor alleles were associated with PTB in this population (P > 0.05). Besides, when the analyses were stratified by gender, none of the alleles of polymorphism in both genders were associated with PTB cases. None of the TLR-8 polymorphisms have associated the risk of developing PTB in Kupang, East Nusa Tenggara population (as opposed to other studies in different ethnic groups). These might reflect the diversity of genetic polymorphisms in eastern Indonesia populations, suggesting different genetic backgrounds with western part of Indonesia.
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TLR-8基因多态性(rs3764880和rs3788935)对印尼库邦肺结核的影响
已知Toll样受体8(TLR-8)是细菌吞噬作用的细胞内信号转导的一部分。结核分枝杆菌(Mtb)是被该受体识别的细胞内致病菌,TLR-8的遗传变异可能改变宿主对肺结核(PTB)的易感性。本研究旨在确定TLR-8基因多态性是否与印度尼西亚库邦的PTB相关。这项病例对照研究比较了115名PTB患者和115名对照组的人口统计学和临床数据,然后使用VeraCode®/BedXpress Illumina®的GoldenGate®基因分型对两种TLR-8单核苷酸多态性(rs3764880和rs3788935)进行了探索。患者和对照组的性别分布没有显著差异。多态性(rs3764880和rs3788935)在该人群中处于Hardy-Weinberg平衡(p>0.05)。PTB患者TLR-8多态性的主要基因型与次要基因型和等位基因的分布如下:rs3764860(GG与GA与AA,50.0%与21.4%与28.6%;G与A,60.9%与39.1%)和rs3788925无等位基因与PTB相关(P>0.05)。此外,按性别分层分析时,两性多态性等位基因均与PTB病例无关。在库邦、东努沙登加拉的人群中,TLR-8多态性均与PTB的发病风险无关(与其他不同种族的研究相反)。这可能反映了印尼东部人群遗传多态性的多样性,表明印尼西部的遗传背景不同。
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审稿时长
12 weeks
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