title: DEFA gene variants associated with IgA nephropathy in a Chinese population.
abstract: IgA nephropathy (IgAN) is a complex syndrome with high genetic heterogeneity. More recently, a genome-wide association study (GWAS) from Southern Han population revealed that variants within 8p23.1, where the DEFA genes encoding a-defensins assembled, were associated with susceptibility to IgAN. To replicate the association and fine-map the genetic variants, a case-control genetic study from an independent Northern Han cohort was conducted. A total of 60 single-nucleotide polymorphisms in a region spanning 350 kb encompassing the DEFA genes cluster were analyzed in 2096 individuals. Copy number variations of DEFA1A3 within the loci were also checked for the independent association. Functional significance of the associated variants was further examined by the in silico method as well as by cis-acting expression quantitative trait loci analysis with mRNA. It showed that 17 out of 60 (28.3%) variants were associated with susceptibility to IgAN. Two independent signals with functional potentials were discovered (rs2738058, P=4.64 × 10(-5), odds ratio (OR)=0.76, 95% confidence interval (CI) 0.66-0.87 and rs9644778, P=4.78 × 10(-3), OR=1.21, 95% CI 1.06-1.39). Besides, marginally significant association of rs9644778 risk genotype with lower proportion of gross hematuria (CC+CA vs AA 35.2% vs 30.2%, P=0.073) was observed. In conclusion, DEFA gene polymorphisms have potentially pathogenic roles in IgAN, and the role of mucosal immunity in the pathogenesis of IgAN has to be emphasized.
authors: 1] Renal Division, Peking University First Hospital, Beijing, People's Republic of China [2] Peking University Institute of Nephrology, Beijing, People's Republic of China [3] Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, People's Republic of China [4] Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, People's Republic of China.
authors: Y Y
authors: YY
authors: Qi
authors: 1] Renal Division, Peking University First Hospital, Beijing, People's Republic of China [2] Peking University Institute of Nephrology, Beijing, People's Republic of China [3] Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, People's Republic of China [4] Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, People's Republic of China.
authors: X J
authors: XJ
authors: Zhou
authors: 1] Renal Division, Peking University First Hospital, Beijing, People's Republic of China [2] Peking University Institute of Nephrology, Beijing, People's Republic of China [3] Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, People's Republic of China [4] Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, People's Republic of China.
authors: F J
authors: FJ
authors: Cheng
authors: 1] Renal Division, Peking University First Hospital, Beijing, People's Republic of China [2] Peking University Institute of Nephrology, Beijing, People's Republic of China [3] Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, People's Republic of China [4] Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, People's Republic of China.
authors: P
authors: P
authors: Hou
authors: 1] Renal Division, Peking University First Hospital, Beijing, People's Republic of China [2] Peking University Institute of Nephrology, Beijing, People's Republic of China [3] Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, People's Republic of China [4] Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, People's Republic of China.
authors: L
authors: L
authors: Zhu
authors: 1] Renal Division, Peking University First Hospital, Beijing, People's Republic of China [2] Peking University Institute of Nephrology, Beijing, People's Republic of China [3] Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, People's Republic of China [4] Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, People's Republic of China.
authors: S F
authors: SF
authors: Shi
authors: 1] Renal Division, Peking University First Hospital, Beijing, People's Republic of China [2] Peking University Institute of Nephrology, Beijing, People's Republic of China [3] Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, People's Republic of China [4] Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, People's Republic of China.
authors: L J
authors: LJ
authors: Liu
authors: 1] Renal Division, Peking University First Hospital, Beijing, People's Republic of China [2] Peking University Institute of Nephrology, Beijing, People's Republic of China [3] Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, People's Republic of China [4] Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, People's Republic of China.
authors: J C
authors: JC
authors: Lv
authors: 1] Renal Division, Peking University First Hospital, Beijing, People's Republic of China [2] Peking University Institute of Nephrology, Beijing, People's Republic of China [3] Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, People's Republic of China [4] Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, People's Republic of China.
authors: H
authors: H
authors: Zhang
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D026281:DEFICIENS Protein / Q000235:genetics*; D056915:DNA Copy Number Variations; D005260:Female; D015870:Gene Expression; D056726:Genetic Association Studies; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D005922:Glomerulonephritis, IGA / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D005810:Multigene Family; D016017:Odds Ratio; D010456:Peptides, Cyclic / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012720:Severity of Illness Index; D023084:alpha-Defensins / Q000235:genetics
chemical_list: C429483:DEFA1A3 protein, human; D026281:DEFICIENS Protein; D010456:Peptides, Cyclic; D023084:alpha-Defensins