FAM167A-BLK基因多态性与类风湿关节炎病情活动的相关性研究

Correlation between FAM167A-BLK gene polymorphism and disease activity of rheumatoid arthritis

目的研究序列相似性家族16酶(FAM167A-BLK)基因多态性与类风湿关节炎(RA)病情活动的相关性。方法本研究为单中心前瞻性队列研究。选取2019年9月至2020年9月河南省人民医院收治的309例RA患者,根据病情活动度分为低活动组162例,男87例,女75例,年龄(45.24±8.33)岁;高活动组147例,男70例,女77例,年龄(44.96±7.01)岁。采用MALDI-TOFMS系统对所选FAMl67A-BLK的4个SNP位点(rs13277113、rs7812879、rs2736340、rs2254546)进行基因分型,分析基因分型质量与Hard-Wemberg平衡检验结果,比较两组各单核苷酸多态性(SNP)位点基因型、等位基因分布情况。结果FAMl67A-BLK的SNP位点rs13277113、rs7812879、rs2736340、rs2254546分型成功率>90%,实验中重复样本分型结果吻合率为100%,各位点均符合Hard-Wemberg平衡检验定律(P=0.512、0.334、0.718、1.000);两组FAMl67A-BLK的SNP位点rs13277113(χ^(2)=6.952,P=0.031)、rs7812879(χ^(2)=15.243,P=0.001)、rs2736340(χ^(2)=7.213,P=0.027)、rs2254546(χ^(2)=9.054,P=0.011)基因型比较,差异均有统计学意义;高活动组FAMl67A-BLKrs13277113位点G等位基因、rs7812879位点T等位基因、rs2736340位点C等位基因、rs2254546位点A等位基因携带者均低于低活动组(χ^(2)=6.922、14.496、5.819、5.234,均P<0.05);高活动组FAMl67A-BLKrs13277113位点G等位基因、rs7812879位点T等位基因、rs2736340位点C等位基因、rs2254546位点A等位基因频率均低于低活动组(均P<0.05)。结论FAMl67A-BLK的SNP位点rs13277113、rs7812879、rs2736340、rs2254546基因型在不同RA病情活动患者中存在显著差异,FAMl67A-BLKrs13277113位点G等位基因、rs7812879位点T等位基因、rs2736340位点C等位基因、rs2254546位点A等位基因与RA病情活动密切相关。

Objective To study the correlation between sequence similarity family 167A-B lymphatic tyrosine kinase(FAM167A-BLK)gene polymorphism and rheumatoid arthritis(RA)disease activity.Methods A total of 309 RA patients admitted to Henan People's Hospital from April 2016 to September 2019 were divided into a low activity group(162 cases)and a high activity group(147 cases)according to their disease activity.The low activity group had 87 males and 75 females,and were(45.24±8.33)year old.The high activity group had 70 males and 77 females,and were(44.96±7.01)years old.The genotypes of the 4 single nucleotide polymorphism(SNP)loci(rs13277113,rs7812879,rs2736340,and rs2254546)were detected by the MALDI-TOF MS system.The genotyping quality and Hard-Wemberg equilibrium test results were analyzed,and the genotypes and allele distributions of the SNP loci were compared between the two groups.Results The SNP loci of FAMl67A-BLK were rs13277113,rs7812879,rs2736340,and rs2254546,and their typing success rates were greater than 90%.In the experiment,the coincidence rate of repeated sample typing results was 100%,and all the points were in accordance with the Hard-Wemberg equilibrium test law(P=0.512,0.334,0.718,and 1.000).There were statistical differences in the genotypes of the 4 SNP loci,rs13277113(χ^(2)=6.952,P=0.031),rs7812879(χ^(2)=15.243,P=0.001),rs2736340(χ^(2)=7.213,P=0.027),and rs2254546(χ^(2)=9.054,P=0.011),of FAMl67A-BLK between the two groups.The carriers of FAMl67A-BLK rs13277113 locus G allele,rs7812879 locus T allele,rs2736340 locus C allele,and rs2254546 locus A allele in the high activity group were lower than those in the low activity group(χ^(2)=6.922,14.496,5.819,and 5.234;all P<0.05).The frequencies of FAMl67A-BLK rs13277113 locus G allele,rs7812879 locus T allele,rs2736340 locus C allele,and rs2254546 locus A allele in the high activity group were lower than those in the low activity group(all P<0.05).Conclusions The genotypes of the SNP loci,rs13277113,rs7812879,rs2736340,and rs2254546,of FAMl67A-BLK are significantly different between patients with different RA conditions.FAM16A-BLK rs13277113 locus G allele,rs7812879 locus T allele,rs2736340 locus C allele,and rs2254546 locus A allele are closely related to RA disease activity.