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溶酶体酸性脂肪酶基因单核苷酸多态性与肺结核易感性。

Lysosomal acid lipase gene single nucleotide polymorphism and pulmonary tuberculosis susceptibility.

机构信息

Department of Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, 110001, Liaoning Province, China; Kalisizo Hospital, Uganda.

Department of Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, 110001, Liaoning Province, China; Kairuki Hospital, Tanzania.

出版信息

Indian J Tuberc. 2021 Apr;68(2):179-185. doi: 10.1016/j.ijtb.2020.07.030. Epub 2020 Aug 5.

Abstract

BACKGROUND

The factors that predispose to pulmonary tuberculosis (PTB) are not fully understood, However. Gene polymorphisms have been associated with PTB development.

OBJECTIVES

In this study, we investigated the relationship between LIPA gene polymorphisms and a predisposition to pulmonary tuberculosis caused by Mycobacterium tuberculosis.

METHODS

A total of 202 cases of PTB and 218 healthy controls (HCS) were included in this study. Analyses were done under allelic, homozygous, and heterozygous, dominant, recessive models, and were used to calculate values, odds ratios (ORs), and 95% confidence intervals (CIs) for assessing the association between single nucleotide polymorphisms (SNPs) and disease risk. Genotyping was conducted using the real time polymerase chain reaction with high resolution melting curve analysis.

RESULTS

When comparing PTB patients with healthy controls (HCS), significant associations with disease development were observed for both SNPs rs1051338 and rs7922269. Analysis was done based on models of genetic inheritance in man that is co-dominant, recessive and dominant models. Rs1051338, the heterozygous (AC vs. AA) P: 0.001, OR: 1.998, 95% CI: 1.312-3.042 and homozygous (CC vs. AA) P: < 0.001, OR: 4.078, 95% CI: 2.134-7.796 Co-dominant associated with increased risk for the disease. Under recessive (CC vs. AA + AC), P: 0.001, OR: 2.829: 95% CI: 1.543-5.185 and dominant model (AC + CC vs. AA) P: < 001, OR: 2.331, 95% CI: 1.564-3.474 the genotypes distribution increased the individual risk, plus its alleles distribution (P: < 0.001, OR: 2.004, 95% CI: 1.505-2.669). Considering SNP rs7922269 mutation significantly increased pulmonary tuberculosis risk as was observed in the homozygous GG vs. TT (P: 0.003, OR: 3.162, 95% CI: 1.431-6.989); heterozygous GT vs. TT (P: < 0.001, OR: 1.2.259, 95% CI: 1.503-3.394); dominant model (GT + GG vs. TT; P: < 0.001, OR: 2.061, 95% CI: 1.402-3.032) and the allele G (P: < 0.001, OR: 1.829, 95% CI:1.361-2.458), however no significant association was observed in the Recessive model (GG vs. TT + GT; P: 0.057, OR: 2.568, 95% CI: 0.965-4.432).

CONCLUSION

The findings of our study strengthen the hypothesis that LIPA rs1051338 and rs7922269 polymorphism associated with increased risk for pulmonary Tb in a sample of northern Chinese population.

摘要

背景

导致肺结核(PTB)的因素尚不完全清楚。然而,基因多态性与结核病的发展有关。

目的

本研究旨在探讨 LIPA 基因多态性与结核分枝杆菌引起的肺结核易感性的关系。

方法

本研究纳入了 202 例肺结核患者和 218 例健康对照者(HCS)。采用等位基因、纯合子、杂合子、显性、隐性模型进行分析,计算单核苷酸多态性(SNP)与疾病风险之间关联的比值比(OR)和 95%置信区间(CI)。采用实时聚合酶链反应高分辨率熔解曲线分析进行基因分型。

结果

与健康对照组(HCS)相比,PTB 患者中 rs1051338 和 rs7922269 两个 SNP 与疾病发展显著相关。分析基于人类遗传模型,包括共显性、隐性和显性模型。rs1051338 杂合子(AC 与 AA)P:0.001,OR:1.998,95%CI:1.312-3.042,纯合子(CC 与 AA)P:<0.001,OR:4.078,95%CI:2.134-7.796,共显性与疾病风险增加相关。在隐性模型(CC 与 AA+AC)P:0.001,OR:2.829,95%CI:1.543-5.185,和显性模型(AC+CC 与 AA)P:<0.001,OR:2.331,95%CI:1.564-3.474,基因型分布增加了个体的患病风险,其等位基因分布(P:<0.001,OR:2.004,95%CI:1.505-2.669)也增加了患病风险。考虑到 SNP rs7922269 突变显著增加了肺结核的风险,与纯合子 GG 与 TT 相比(P:0.003,OR:3.162,95%CI:1.431-6.989);杂合子 GT 与 TT 相比(P:<0.001,OR:1.2259,95%CI:1.503-3.394);显性模型(GT+GG 与 TT;P:<0.001,OR:2.061,95%CI:1.402-3.032)和等位基因 G(P:<0.001,OR:1.829,95%CI:1.361-2.458),然而在隐性模型(GG 与 TT+GT;P:0.057,OR:2.568,95%CI:0.965-4.432)中未观察到显著关联。

结论

本研究结果支持 LIPA rs1051338 和 rs7922269 多态性与中国北方人群肺结核易感性增加的假说。

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