HLA-DRB1*15:01 and HLA-DRB3*02:02 in PLA2R-Related Membranous Nephropathy
HLA-DRB1*15:01 and HLA-DRB3*02:02 in PLA2R-Related Membranous Nephropathy
复制标题
PLA2R 相关膜性肾病中的 HLA-DRB115:01 和 HLA-DRB302:02。
DOI：
10.1681/asn.2016060644
复制
发表时间：
2017-05-01
影响因子：
13.6
通讯作者：
Liu, Zhi-Hong
中科院分区：
文献类型：
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作者：
Le, Wei-Bo;Shi, Jing-Song;Liu, Zhi-Hong
特发性膜性肾病（MN）与HLA相关，然而，涉及的HLA等位基因仍不清楚。为了确定中国人群中与磷脂酶A2受体（PLA 2 R）相关MN相关的HLA风险等位基因，我们对99例PLA 2 R相关MN患者、50例PLA 2 R无关MN患者和100例健康受试者的DNA样本中的整个MHC区域进行了测序。两个HLA风险等位基因，HLA-DRB 1 *15：01和HLA-DRB 3 *02：02，独立且强烈地与PLA 2 R相关MN的风险增加相关。在调整HLA-DRB 1 *15：01和HLA-DRB 3 *02：02后，没有其他等位基因显示与PLA 2 R相关的MN显著相关。对293名患有PLA 2 R相关MN的参与者和285名健康对照的独立队列进行的复制研究验证了这些发现。在联合分析中，多变量逻辑回归模型证实HLA-DRB 1 *15：01（比值比[OR]，24.9; 95%置信区间[95%CI]，15.3至42.6; P=2.3x10（-35））和HLA-DRB 3 *02：02（OR，17.7; 95%CI，11.0至30.3; P=8.0x10（-29））与PLA 2 R相关MN独立且强烈相关。与43.9%的对照组相比，多达98.7%的PLA 2 R相关MN患者携带至少一个HLA风险等位基因。与没有危险等位基因的受试者相比，具有任一危险等位基因的受试者发生PLA 2 R相关MN的几率更高（OR，98.9; 95%CI，44.4至281.7; P=2.5x10（-23））。这些HLA风险等位基因也与PLA 2 R相关MN患者的发病年龄相关。总之，我们的研究结果提供了明确的证据表明，HLA-DRB 1 *15：01和HLA-DRB 3 *02：02等位基因独立和强烈地与中国人群中PLA 2 R相关的MN。
Idiopathic membranous nephropathy (MN) is associated with HLA; however, the HLA allele involved remains unknown. To identify the HLA risk alleles associated with phospholipase A2 receptor (PLA2R)-related MN in the Chinese population, we sequenced the entire MHC region in DNA samples from 99 patients with PLA2R-related MN, 50 patients with PLA2R-unrelated MN, and 100 healthy subjects. Two HLA risk alleles, HLA-DRB1*15:01 and HLA-DRB3*02:02, independently and strongly associated with an increased risk of PLA2R-related MN. After adjusting for HLA-DRB1*15:01 and HLA-DRB3*02:02, no other alleles showed significant association with PLA2R-related MN. A replication study in an independent cohort of 293 participants with PLA2R-related MN and 285 healthy controls validated these findings. In a joint analysis, a multivariate logistic regression model confirmed that HLA-DRB1*15:01 (odds ratio [OR], 24.9; 95% confidence interval [95% Cl], 15.3 to 42.6; P=2.3x10(-35)) and HLA-DRB3*02:02 (OR, 17.7; 95% CI, 11.0 to 30.3; P=8.0x10(-29)) independently and strongly associated with PLA2R-related MN. As many as 98.7% of patients with PLA2R-related MN, compared with 43.9% of control subjects, carried at least one HLA risk allele. Subjects with either risk allele had higher odds of developing PLA2R-related MN than those without a risk allele (OR, 98.9; 95% CI, 44.4 to 281.7; P=2.5x10(-23)). These HLA risk alleles also associated with the age at disease onset in patients with PLA2R-related MN. In conclusion, our findings provide clear evidence that the HLA-DRB1*15:01 and HLA-DRB3*02:02 alleles independently and strongly associate with PLA2R-related MN in the Chinese population.