评估中国西北地区汉族人群白细胞介素-1β（IL-1B）基因变异及其与骨质疏松易感性的相互作用。

Evaluation of genetic variants in IL-1B and its interaction with the predisposition of osteoporosis in the northwestern Chinese Han population.

机构信息

State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China.

Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, Northwest University, Xi'an, Shaanxi, China.

出版信息

J Gene Med. 2020 Oct;22(10):e3214. doi: 10.1002/jgm.3214. Epub 2020 Jun 7.

DOI:10.1002/jgm.3214

PMID:32391643

Abstract

BACKGROUND

Interleukin (IL)-1β stimulates the proliferation and differentiation of osteoclast precursors into mature osteoclasts. IL-1B polymorphisms may influence the gene and protein expression of IL-1β. The present study aimed to investigate the association of IL-1B variants (rs2853550, rs1143643, rs3136558, rs1143630, rs1143627, rs16944 and rs1143623) and their interaction with osteoporosis risk among the northwestern Chinese Han population.

METHODS

AN Agena MassARRAY system (Agena, San Diego, CA, USA) was employed for genotyping in 594 osteoporosis patients and 599 healthy controls. The possible association between IL-1B polymorphisms and risks of osteoporosis development was identified with odds ratios (OR) and 95% confidence intervals (CI) using logistic regression models. Haplotype analysis and multifactor dimension reduction analysis were used to explore the potential association between combined single nucleotide polymorphisms (SNPs) and osteoporosis risk.

RESULTS

The AA genotype of rs2853550 was a protective factor for osteoporosis occurrence (OR = 0.11, p = 0.038), whereas rs16944 (OR = 1.19, p = 0.037) and rs1143623 (OR = 1.21, p = 0.025) conferred an increased risk of osteoporosis. Moreover, rs1143627, rs16944 and rs1143623 were associated with an elevated susceptibility to osteoporosis, especially in females and individuals aged > 60 years or with a body mass index > 24 kg/m . Haplotype G A G was a risk factor of osteoporosis occurrence (OR = 1.20, p = 0.032). The best model of SNP-SNP analysis was a four-locus combination of rs1143643, rs3136558, rs1143630 and rs1143623 (testing accuracy = 0.5623).

CONCLUSIONS

IL-1B polymorphisms and haplotype G A G might contribute to susceptibility to osteoporosis. The SNP-SNP interaction of polymorphisms in IL-1B revealed the accumulated effect on osteoporosis risk.

摘要

背景

白细胞介素（IL）-1β刺激破骨细胞前体增殖和分化为成熟的破骨细胞。IL-1B 多态性可能影响 IL-1β 的基因和蛋白表达。本研究旨在探讨白细胞介素 1B 变异（rs2853550、rs1143643、rs3136558、rs1143630、rs1143627、rs16944 和 rs1143623）及其与中国西北汉族人群骨质疏松症风险的相互作用。

方法

采用 Agena MassARRAY 系统（Agena，圣地亚哥，加利福尼亚州，美国）对 594 例骨质疏松症患者和 599 例健康对照进行基因分型。采用 logistic 回归模型，用比值比（OR）和 95%置信区间（CI）确定白细胞介素 1B 多态性与骨质疏松症发生风险的关联。采用单核苷酸多态性（SNP）单体型分析和多因素降维分析探讨联合 SNP 与骨质疏松症风险的潜在关联。

结果

rs2853550 的 AA 基因型是骨质疏松发生的保护因素（OR = 0.11，p = 0.038），而 rs16944（OR = 1.19，p = 0.037）和 rs1143623（OR = 1.21，p = 0.025）则增加了骨质疏松的风险。此外，rs1143627、rs16944 和 rs1143623 与骨质疏松易感性增加有关，尤其是在女性和年龄 > 60 岁或体重指数 > 24 kg/m 的个体中。单体型 G A G 是骨质疏松发生的危险因素（OR = 1.20，p = 0.032）。SNP-SNP 分析的最佳模型是 rs1143643、rs3136558、rs1143630 和 rs1143623 四个基因座的组合（检验准确率 = 0.5623）。