The association between variants in PLA2R and HLA-DQA1 and renal outcomes in patients with primary membranous nephropathy in Western China.
The association between variants in PLA2R and HLA-DQA1 and renal outcomes in patients with primary membranous nephropathy in Western China.
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中国西部原发性膜性肾病患者PLA 2 R和HLA-DQA 1变异与肾脏预后的关系
DOI：
10.1186/s12920-021-00969-0
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发表时间：
2021-05-08
影响因子：
2.7
通讯作者：
Wang W
中科院分区：
文献类型：
--
作者：
Fan S;Wang Q;Wang AY;Zhang P;Zhong X;Chen S;Li G;Wang L;Wang W
全基因组关联和我们之前的研究表明，m型磷脂酶A2受体（PLA2R）和人白细胞抗原复合体II类hla - dq α-链1 （HLA-DQA1）基因的单核苷酸多态性（snp）被鉴定为与原发性膜性肾病（PMN）相关。然而，这些snp是否影响PMN患者的临床表现和肾脏预后尚不清楚。在这里，我们评估了这些snp与PMN的临床表现和肾脏结局之间是否存在关联。在我们的研究中选择了PLA2R中的7个SNP和HLA-DQA1中的1个SNP。收集了314例PMN患者的临床资料，并评估了基因型与表型之间的关系。共有186名患者有随访数据。在中位随访18.6个月后，我们评估了这些基因多态性患者的治疗反应和肾脏预后。8个snp与PMN患者临床表现无相关性（Pc < 0.05）。rs3828323 T等位基因与高血压有极显著相关性（P = 0.008, Pc = 0.064, OR = 1.821）。治疗后中性粒细胞,SR集团(包括CR和公关)血清肌酐水平较低(68.4±18.8μmol / L和122.8±126.6μmol / L, P < 0.001),尿素(5.5±1.9更易更易/ L L和8.0±4.0,P < 0.001),尿酸(358.5±95.1μmol / L和392.8±118.1μmol / L, P = 0.037)和尿蛋白(0.23 g / d(0.76, 1.05)和3.01 g / d (2.06, 7.95), P < 0.001),更高的表皮生长因子受体(100.0±20.1 ml / min / 1.73平方米和77.1±35.3 ml / min / 1.73平方米,P < 0.001)和白蛋白(41.1±5.1 g / L vs.30.4±8.2 g / L, P < 0.001)。我们还发现，CT/TT基因型rs3828323的PMN患者的累积生存率高于CC基因型患者。Rs3828323可能影响PMN患者的高血压和肾脏预后。这种基因型-疾病表型关联的机制有待进一步研究。在线版本包含补充材料，可在10.1186/s12920-021-00969-0获得。
Both Genome-wide associations and our previous study have shown that single nucleotide polymorphisms (SNPs) of M-type phospholipase A2 receptor (PLA2R) and human leukocyte antigen complex class II HLA-DQα-chain 1 (HLA-DQA1) gene were identified to be associated with primary membranous nephropathy (PMN). However, whether these SNPs affect clinical manifestation and renal outcome for PMN patients is poorly defined. Here, we evaluated whether there is an association between these SNPs and clinical manifestations and renal outcomes of PMN in a western Chinese cohort. Seven SNPs within PLA2R and one SNP in HLA-DQA1 were selected in our study. Clinical data from 314 patients with PMN were collected and the relationship between the genotype and phenotype was evaluated. A total of 186 patients had follow-up data. We assessed the treatment responses and renal outcomes between patients with these gene polymorphisms after a median follow-up of 18.6 months. Eight SNPs were not associated with clinical manifestations of PMN patients (Pc < 0.05). rs3828323 T allele was marginally significantly associated with hypertension (P = 0.008, Pc = 0.064, OR = 1.821). After treatment for PMN, the SR group (including CR and PR) had lower serum creatinine level (68.4 ± 18.8 μmol/L vs. 122.8 ± 126.6 μmol/L, P < 0.001), urea (5.5 ± 1.9 mmol/L vs. 8.0 ± 4.0 mmol/L, P < 0.001), uric acid (358.5 ± 95.1 μmol/L vs. 392.8 ± 118.1 μmol/L, P = 0.037) and urinary protein (0.23 (0.76,1.05) g/d vs. 3.01 (2.06,7.95) g/d, P < 0.001), higher eGFR (100.0 ± 20.1 ml/min/1.73m2 vs. 77.1 ± 35.3 ml/min/1.73m2, P < 0.001) and albumin (41.1 ± 5.1 g/L vs.30.4 ± 8.2 g/L, P < 0.001). We also identified that PMN patients with CT/TT genotype for rs3828323 achieved higher cumulative survival rate than patients with CC genotype. Rs3828323 may influence hypertension and renal outcome in patients with PMN. Further research is needed to explore the mechanism for this genotype-disease phenotype association. The online version contains supplementary material available at 10.1186/s12920-021-00969-0.
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