title: Single-nucleotide polymorphisms in the PLA2R1 gene are associated with systemic lupus erythematosus and lupus nephritis in a Chinese Han population.
abstract: Several novel susceptibility genes for systemic lupus erythematosus (SLE) and other nephropathy have been identified in recent genome-wide association studies. Membranous nephropathy is the most common diagnosis in adults with the nephrotic syndrome, and both idiopathic membranous nephropathy (IMN) and lupus nephritis (LN) are autoimmune diseases of the kidney; they may share common disease mechanisms that overlap with genetic susceptibility. Therefore, we sought to identify genetic variants associated with IMN in SLE/LN. The PLA2R1 single-nucleotide polymorphisms rs4664308, rs3828323, rs3792189, and rs3792192 were genotyped in a cohort of 1247 SLE patients and 1174 healthy controls, using the Sequenom MassArray system method. PLA2R1 displayed a nominally significantly genetic association with SLE [for rs4664308, P = 0.02, odds ratio (OR) 1.16, 95 % confidence interval (CI) 1.02-1.31; for rs3792192, P = 7.9 × 10(-3), OR 1.18, 95 % CI 1.05-1.34] and LN (for rs4664308, P = 0.04). The frequencies of genotypes of rs3792189 and rs3828323 were significantly different between the SLE patients and controls (all P < 0.05), and the haplotype (AA) formed by rs3792189 and rs3792192 was associated with SLE (P = 0.019). This was the first study to reveal that PLA2R1 polymorphisms were associated with SLE/LN patients, indicating that PLA2R1 might be a susceptibility gene for SLE/LN in a Chinese Han population.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.|Department of Rheumatology, The Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Aihong
authors.initials: A
authors.lastname: Zhou
authors.affiliation: Beijing DNALead Co.LTD, Beijing, China.
authors.forename: Guanting
authors.initials: G
authors.lastname: Lv
authors.affiliation: Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.|Department of Clinical Laboratory, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Si
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Wen
authors.affiliation: Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.
authors.forename: Ziyan
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.
authors.forename: Shulan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Rheumatology, The Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Jibo
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.
authors.forename: Fengchun
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China. yongzhelipumch@126.com.
authors.forename: Yongzhe
authors.initials: Y
authors.lastname: Li
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002681:China; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008181:Lupus Nephritis / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D054507:Receptors, Phospholipase A2 / Q000235:genetics*
chemical_list: C516360:PLA2R1 protein, human; D054507:Receptors, Phospholipase A2
keywords: LN; PLA2R1; Risk; SLE; SNPs