M型磷脂酶A_2受体和人类白细胞抗原基因单核苷酸多态性与维吾尔族特发性膜性肾病的相关性

Association of PLA_2R and HLA-DQA1 gene single nucleotide polymorphism with idiopathic membranous nephropathy in Uygur patients

目的探讨M型磷脂酶A_2受体(M-type phospholipase A_2receptor,PLA_2R)rs35771982和人类白细胞抗原(human leukocyte antigen DQα-chain 1,HLA-DQA1)rs2187668位点单核苷酸多态性与维吾尔族特发性膜性肾病(idiopathic membranous nephropathy,IMN)的相关性。方法 45例维吾尔族IMN患者为IMN组,45例同期维吾尔族体检健康者为对照组,采用直接测序法检测2组PLA_2R基因rs35771982、HLA-DQA1基因rs2187668位点单核苷酸多态性(single nucleotide polymorphism,SNP),比较2组基因型和等位基因频率;采用单因素logistic回归分析风险基因型。结果 IMN组PLA_2R基因rs35771982位点C等位基因频率(78.90%)明显高于对照组(40.00%)(P<0.01);在显性模型下PLA_2R基因rs35771982位点携带CC基因型的患病风险为携带CG+GG基因型的7倍(OR=7.00,95%CI:2.74~17.87,P=0.000),隐性模型下携带GG基因型的患病风险为携带CC+CG基因型的0.13倍(OR=0.13,95%CI:0.04~0.44,P=0.000);IMN组PLA_2R基因rs35771982位点CC基因型血清肌酐[103.15(74.28,175.67)μmol/L]和24h尿蛋白[2.77(2.00,3.95)g]明显高于CG+GG基因型[73.70(58.87,106.65)μmol/L、1.90(1.39,2.75)g](P<0.05),收缩压[(138.03±23.11)mmHg]高于CG+GG基因型[(123.13±15.05)mmHg],血清白蛋白[26.80(17.84,28.86)g/L]明显低于CG+GG基因型[29.96(25.67,36.64)g/L](P<0.05);2组HLA-DQA1SNP rs2187668位点仅检测到GG基因型,未检测到GA、AA基因型。结论 PLA_2R基因rs35771982位点CC基因型和C等位基因是新疆维吾尔族IMN的易感基因,也是功能基因,其中CC基因型与尿蛋白定量呈正相关,与血清白蛋白水平呈负相关。

Objective To investigate the correlations of M-type phospholipase A2 receptor （PLA2R） rs35771982 and human leukocyte antigen （HLA-DQA1） rs2187668 single nucleotide polymorphism with idiopathic membranous nephropathy （IMN） in Uygur patients. Methods Forty-five Uygur patients with IMN （IMN group） and 45 Uygur healthy controls （control group） were determined the single nucleotide polymorphisms （SNP） of rs35771982 in PLA2R and rs2187668 in HLA-DQA1 gene with direct sequencing to compare the genotype and gene allele frequency between two groups. The risk genotype was analyzed with univariate regression analysis. Results The allelic frequency for rs35771982 locus C gene was significantly higher in IMN group （78.90%） than that in control group （40.00%） （P〈0.01）. In the dominant model, the risk for IMN in patients carrying CC genotype at rs35771982 was 7 times as high as that in patients carrying CG＋GGgenotype （0R=7.00, 95%CI： 2.74-17.87, P=0.000）. In the recessive model, the risk for IMN in patients carrying GG genotype at rs35771982 was 0.13 times as high as that in patients carrying CC＋CG genotype （OR： 0.13, 95%CI： 0. 04-0.44, P=0. 000）. The levels of serum albumin and 24 h urine protein were significantly higher in patients with CC genotype at PLA2R rs35771982 （（103. 15 （74. 28, 175. 67） μmol/L, 2. 77 （2.00, 3. 95） g/d） than those in patients with CG-GG genotype （73.70 （58.87, 106.65） μmol/L, 1.90 （1.39, 2.75） g/d） in IMN group （P〈 0.05）. The systolic blood pressure （（138.03 ±23. 11） mm Hg ） was significantly higher and serum albumin （26. 80 （17.84, 28.86） g/L） was significantly lower in patients with CC genotype at PLA2R rs35771982 than those in patients with CG＋GG genotype （（123. 13±15. 05） mm Hg, 29. 96 （25. 67, 36. 64） g/L） in IMN group （P〈0.05）. HLA-DQA1 SNP rs2187668 locus was detected only GG genotype, and no GA or AA genotype in two groups. Conclusion The CC genotype and C allele at rs35771982 in PLA2R gene are both susceptibility and functional genes in Uygur IMN patients in Xinjiang, and CC genotype is positively correlated with urine protein quantitation and is negatively correlated with serum albumin level.