BACKGROUND AND OBJECTIVES: One hypothesis states that IgA nephropathy (IgAN) is a syndrome with an autoimmune component. Recent studies strongly support the notion of shared genetics between immune-related diseases. This study investigated single-nucleotide polymorphisms (SNPs) reported to be associated with systemic lupus erythematosus (SLE) in a Chinese cohort of patients with IgAN and in controls. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study investigated whether SNP markers that had been reported to be associated with SLE were also associated with IgAN in a Chinese population. The study cohort consisted of 1194 patients with IgAN and 902 controls enrolled in Peking University First Hospital from 1997 to 2008. RESULTS: Ninety-six SNPs mapping to 60 SLE loci with reported P values <1 × 10(-5) were investigated. CFH (P=8.41 × 10(-6)), HLA-DRA (P=4.91 × 10(-6)), HLA-DRB1 (P=9.46 × 10(-9)), PXK (P=3.62 × 10(-4)), BLK (P=9.32 × 10(-3)), and UBE2L3 (P=4.07 × 10(-3)) were identified as shared genes between IgAN and SLE. All associations reported herein were corroborated by associations at neighboring SNPs. Many of the alleles that are risk alleles for SLE are protective alleles for IgAN. By analyses of two open independent expression quantitative trait loci (eQTL) databases, correlations between genotypes and corresponding gene expression were observed (P<0.05 in multiple populations), suggesting a cis-eQTL effect. From gene-expression databases, differential expressions of these genes were observed in IgAN. Additive interactions between PXK rs6445961 and HLA-DRA rs9501626 (P=1.51 × 10(-2)), as well as multiplicative interactions between CFH rs6677604 and HLA-DRB1 rs9271366 (P=1.77 × 10(-2)), and between HLA-DRA rs9501626 and HLA-DRB1 rs9271366 (P=3.23 × 10(-2)) were observed. Disease risk decreased with accumulation of protective alleles. Network analyses highlighted four pathways: MHC class II antigen presentation, complement regulation, signaling by the B-cell receptor, and ubiquitin/proteasome-dependent degradation. CONCLUSION: From this "systems genetics" perspective, these data provide important clues for future studies on pleiotropy in IgAN and lupus nephritis.
BACKGROUND AND OBJECTIVES: One hypothesis states that IgA nephropathy (IgAN) is a syndrome with an autoimmune component. Recent studies strongly support the notion of shared genetics between immune-related diseases. This study investigated single-nucleotide polymorphisms (SNPs) reported to be associated with systemic lupus erythematosus (SLE) in a Chinese cohort of patients with IgAN and in controls. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study investigated whether SNP markers that had been reported to be associated with SLE were also associated with IgAN in a Chinese population. The study cohort consisted of 1194 patients with IgAN and 902 controls enrolled in Peking University First Hospital from 1997 to 2008. RESULTS: Ninety-six SNPs mapping to 60 SLE loci with reported P values <1 × 10(-5) were investigated. CFH (P=8.41 × 10(-6)), HLA-DRA (P=4.91 × 10(-6)), HLA-DRB1 (P=9.46 × 10(-9)), PXK (P=3.62 × 10(-4)), BLK (P=9.32 × 10(-3)), and UBE2L3 (P=4.07 × 10(-3)) were identified as shared genes between IgAN and SLE. All associations reported herein were corroborated by associations at neighboring SNPs. Many of the alleles that are risk alleles for SLE are protective alleles for IgAN. By analyses of two open independent expression quantitative trait loci (eQTL) databases, correlations between genotypes and corresponding gene expression were observed (P<0.05 in multiple populations), suggesting a cis-eQTL effect. From gene-expression databases, differential expressions of these genes were observed in IgAN. Additive interactions between PXKrs6445961 and HLA-DRArs9501626 (P=1.51 × 10(-2)), as well as multiplicative interactions between CFHrs6677604 and HLA-DRB1rs9271366 (P=1.77 × 10(-2)), and between HLA-DRArs9501626 and HLA-DRB1rs9271366 (P=3.23 × 10(-2)) were observed. Disease risk decreased with accumulation of protective alleles. Network analyses highlighted four pathways: MHC class II antigen presentation, complement regulation, signaling by the B-cell receptor, and ubiquitin/proteasome-dependent degradation. CONCLUSION: From this "systems genetics" perspective, these data provide important clues for future studies on pleiotropy in IgAN and lupus nephritis.
Authors: John Feehally; Martin Farrall; Anne Boland; Daniel P Gale; Ivo Gut; Simon Heath; Ashish Kumar; John F Peden; Patrick H Maxwell; David L Morris; Sandosh Padmanabhan; Timothy J Vyse; Anna Zawadzka; Andrew J Rees; Mark Lathrop; Peter J Ratcliffe Journal: J Am Soc Nephrol Date: 2010-07-01 Impact factor: 10.121
Authors: Julia Bontscho; Adrian Schreiber; Rudolf A Manz; Wolfgang Schneider; Friedrich C Luft; Ralph Kettritz Journal: J Am Soc Nephrol Date: 2011-01-13 Impact factor: 10.121
Authors: Wanling Yang; Nan Shen; Dong-Qing Ye; Qiji Liu; Yan Zhang; Xiao-Xia Qian; Nattiya Hirankarn; Dingge Ying; Hai-Feng Pan; Chi Chiu Mok; Tak Mao Chan; Raymond Woon Sing Wong; Ka Wing Lee; Mo Yin Mok; Sik Nin Wong; Alexander Moon Ho Leung; Xiang-Pei Li; Yingyos Avihingsanon; Chun-Ming Wong; Tsz Leung Lee; Marco Hok Kung Ho; Pamela Pui Wah Lee; Yuk Kwan Chang; Philip H Li; Ruo-Jie Li; Lu Zhang; Wilfred Hing Sang Wong; Irene Oi Lin Ng; Chak Sing Lau; Pak Chung Sham; Yu Lung Lau Journal: PLoS Genet Date: 2010-02-12 Impact factor: 5.917
Authors: Elin Grundberg; Veronique Adoue; Tony Kwan; Bing Ge; Qing Ling Duan; Kevin C L Lam; Vonda Koka; Andreas Kindmark; Scott T Weiss; Kelan Tantisira; Hans Mallmin; Benjamin A Raby; Olle Nilsson; Tomi Pastinen Journal: PLoS Genet Date: 2011-01-20 Impact factor: 5.917