HMGB1基因多态性与豫北地区肺结核易感性的相关性

Association between high-mobility group box 1 protein gene polymorphism and susceptibility to pulmonary tuberculosis in northern Henan

摘要:

目的 探讨高迁移率族蛋白1（HMGB1）单核苷酸多态性与豫北地区肺结核患者易感性的相关性。方法 选取2017年1-12月新乡医学院第一附属医院被确诊为肺结核的320例患者为结核组，该院同时期300名健康体检者为对照组。采用PCR技术和Sanger测序对结核组和对照组的HMGB1 rs1412125（-1615A/G）、rs1045411（+1177G/A）、rs2249825（+3814C/G）位点进行基因分型，通过对两组等位基因频率、基因型频率及四种遗传模型（共显性、显性、隐性和超显性）分析，研究HMGB1基因多态性与肺结核的易感性。结果 所有位点的基因型分布均符合Hardy-Weinberg平衡。两组间+1177G/A位点等位基因频率差异具有统计学意义（OR=1.485，95% CI：1.110~1.986，P=0.007），其基因型分布差异也具有统计学意义（P<0.05）；+1177G/A位点的共显性模型中，与GG基因型相比，AG基因型（OR=1.447，95% CI：1.025~2.041，P=0.035）和AA基因型（OR=2.812，95% CI：0.985~8.033，P=0.045）与肺结核的易感性相关；+1177G/A位点的显性模型[（AG+AA）vs GG，OR=1.524，95% CI：1.090~2.131，P=0.014]也与肺结核的易感性相关；在+1177G/A位点的隐性模型和超显性模型中，两组间差异无统计学意义（P>0.05）。在-1615A/G和+3814C/G位点两组间等位基因及基因型分布差异均无统计学意（P>0.05）。结论 HMGB1基因rs1045411（+1177G/A）位点多态性可能与肺结核的易感性相关，其等位基因A可能是肺结核的易感基因，携带rs1045411（+1177G/A）A等位基因可能增加患肺结核的风险。

Abstract:

Objective To explore the correlation between single nucleotide polymorphisms(SNPs) of high-mobility group box 1 protein (HMGB1) and susceptibility of pulmonary tuberculosis(PTB) patients in northern Henan. Methods 320 patients who were diagnosed with PTB in the First Affiliated Hospital of Xinxiang Medical University from January to December 2017 were selected as the tuberculosis group, and 300 healthy people who underwent physical examination during the same period were selected as the control group. Genotyping of HMGB1 rs1412125(-1615A/G), rs1045411(+1177G/A) and rs2249825(+3814C/G) loci in tuberculosis group and control group was performed by PCR and Sanger sequencing. Association between HMGB1 gene polymorphism and susceptibility to PTB in two groups was studied with allele frequency, genotype frequency, and four genetic models (co-dominance, dominance, recessiveness and over-dominance). Results Genotype distribution of all loci conformed to Hardy-Weinberg equilibrium. There was significant difference in allele frequency at +1177G/A locus between two groups (OR, 1.485[95%CI, 1.110-1.986], P=0.007), there was significant difference in genotype distribution between two groups (P<0.05); in the co-dominance model of 1177G/A locus, AG genotype (OR,1.447[95% CI, 1.025-2.041], P=0.035) and AA genotype (OR, 2.812[95%CI, 0.985-8.033], P=0.045) were associated with susceptibility to PTB compared with GG genotype; the dominant model of +1177G/A locus ([AG+AA] vs GG, OR, 1.524[95% CI, 1.090-2.131], P=0.014) was also associated with the susceptibility to PTB; there was no significant difference between the recessive model and the over-dominant model of +1177G/A locus (P>0.05). There was no significant difference in allele and genotype distribution between -1615A/G and +3814C/G loci (P>0.05). Conclusion The polymorphism of rs1045411 (+1177G/A) of HMGB1 gene may be associated with the susceptibility to PTB, allele A of HMGB1 gene may be a susceptible gene of PTB, and carrying of rs1045411(+1177G/A) allele A may increase the risk of developing PTB.