ESRRB rs12437118多态性与中国华北汉族人群结核病易感性的关系

Association of ESRRB rs12437118 polymorphisms with tuberculosis susceptibility of Han population in northern China

目的:调查ESRRB编码基因ESRRB内的rs12437118多态性与中国华北汉族人群结核病易感性的关系。方法:收集2018年3月至2019年10月于首都医科大学附属北京胸科医院就诊的籍贯信息为华北地区的607例汉族结核病患者作为病例组,以及660名籍贯信息为华北地区的结核病专科医院的汉族工作人员作为健康对照组。采用竞争性等位基因特异性PCR(kompetitive allele-specific PCR,KASP)测定ESRRB基因rs12437118位点的单核苷酸多态性(SNP)。ESRRB蛋白的血清水平通过酶联免疫吸附测定法检测。通过比对基因型和ESRRB蛋白的差异,分析ESRRB基因rs12437118位点多态性与结核病易感性的关系。使用不同的遗传模型(包括显性和隐性模型)评估ESRRB rs12437118多态性与结核病的关联。结果:GG、GA和AA rs12437118基因型频率在病例组中分别为50.2%(305/607)、38.1%(231/607)和11.7%(71/607),在健康对照组中分别为44.9%(296/660)、45.6%(301/660)和9.5%(63/660),两组比较差异有统计学意义(χ^(2)=7.619,P=0.022)。GA rs12437118 SNP基因型与华北地区汉族人群结核病低风险明显相关[OR(95%CI)=1.34(1.06~1.70),χ^(2)=6.079,P=0.014]。病例组血清ESRRB水平[243.1(174.3,367.3)pg/μl],明显低于健康对照组血清ESRRB水平[360.3(240.0,604.1)pg/μl],差异有统计学意义(Z=5.623,P<0.001)。病例组AA、GA、GG基因型的ESRRB水平分别为328.9(226.3,553.0)pg/μl、232.6(164.7,379.7)pg/μl、196.8(150.1,328.4)pg/μl,差异无统计学意义(F=1.790,P=0.171);对照组AA、GA、GG基因型的ESRRB水平分别为427.5(253.9,619.4)pg/μl、353.7(247.8,666.4)pg/μl、303.3(219.8,519.1)pg/μl,差异无统计学意义(F=1.751,P=0.177)。结论:中国华北地区的汉族人群中ESRRB rs12437118 GA基因型与结核病易感性之间存在明显关联性,ESRRB在结核病患者人群血清中的低表达与rs12437118基因多态性无关。

Objective:To investigate the relationship between rs12437118 polymorphisms in ESRRB-coding gene ESRRB and tuberculosis susceptibility in Han population in northern China.Methods:A total of 607 Han tuberculosis patients in northern China visited Beijing Chest Hospital affiliated to Capital Medical University from March 2018 to October 2019(the case group)and 660 Han staff of tuberculosis specialist hospitals in northern China(the health control group)were collected.Competitive allele-specific PCR(KASP)was used to determine the polymorphism of the ESRRB gene rs12437118 single nucleotide polymorphism(SNP).Serum levels of ESRRB protein were measured by enzyme-linked immunosorbent assay(ELISA).By comparing the differences between genotype and ESRRB protein,the relationship between ESRRB gene rs12437118 locus polymorphisms and tuberculosis susceptibility was analyzed.The association of ESRRB rs12437118 polymorphisms with tuberculosis was evaluated using different genetic models,including dominant and recessive models.Results:The frequencies of GG,GA and AA rs12437118 genotypes were 50.2%(305/607),38.1%(231/607)and 11.7%(71/607)in the case group and 44.9%(296/660),45.6%(301/660)and 9.5%(63/660)in the healthy control group,respectively,and the difference between the two groups was statistically significant(χ^(2)=7.619,P=0.022).GA rs12437118 SNP genotype was significantly associated with a low risk of tuberculosis in the Han population in northern China(OR(95%CI)=1.34(1.06-1.70),χ^(2)=6.079,P=0.014).The serum ESRRB level in the case group(243.1(174.3,367.3)pg/μl)was significantly lower than that in the healthy control group(360.3(240.0,604.1)pg/μl)(Z=5.623,P<0.001).However,there were no significant difference in ESRRB levels with different rs12437118 genotypes between the case group and the control group.ESRRB levels of AA,GA and GG genotypes in the case group were 328.9(226.3,553.0)pg/μl,232.6(164.7,379.7)pg/μl and 196.8(150.1,328.4)pg/μl,respectively(F=1.790,P=0.171);and in the control group were 427.5(253.9,619.4)pg/μl,353.7(247.8,666.4)pg/μl and 303.3(219.8,519.1)pg/μl,respectively(F=1.751,P=0.177).Conclusion:There was a significant association between ESRRB rs12437118 GA genotype and tuberculosis susceptibility in Han population in northern China,and low expression of ESRRB in serum of tuberculosis patients was not associated with rs12437118 gene polymorphism.