title: Polymorphism of DEFA in Chinese Han population with IgA nephropathy.
abstract: Our recent genome-wide association study (GWAS) had discovered a new locus at 8p23 (rs2738048) associated with IgA nephropathy (IgAN) in Chinese Han patients, implicating the DEFA gene family within this locus as susceptibility genes. However, it is still unknown whether there are additional variations within these genes associated with the disease susceptibility. The aim of this study is to investigate the polymorphisms of DEFA genes in the susceptibility to IgAN and explore possible disease mechanisms. Sixteen tag single-nucleotide polymorphisms (tag SNPs) were selected for association study in 1,000 IgAN cases and 1,000 controls by using Sequenom MassArray system or TaqMan SNP genotyping assays. We found seven SNPs within DEFA genes that were significantly associated with IgAN, including rs2738048 discovered in our previous GWAS (p = 0.0007, OR = 0.77) and additional 6 SNPs (rs2615787, p = 0.0001, OR = 0.74; rs2738081, p = 0.0003, OR = 0.72; rs2738058, p = 0.0001, OR = 0.73; rs4288398, p = 0.0008, OR = 0.78; rs6984215, p = 0.002, OR = 0.63; rs12716641, p = 0.00002, OR = 0.71). Electrophoretic mobility shift assays and luciferase assays demonstrated that fragments containing rs2738048, rs2738081 and rs6984215 were transcription factor binding sites for CTF, SP1 and CdxA, respectively, and the allele status of rs2738048 and rs6984215 could significantly change the luciferase activity. These results suggest that polymorphisms within DEFA genes are involved in gene transcriptional regulation, and this may have some effect in mediating susceptibility to IgAN in southern Chinese.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, 58th, Zhongshan Road II, Guangzhou, 510080, Guangdong, China.
authors.forename: Ricong
authors.initials: R
authors.lastname: Xu
authors.forename: Shaozhen
authors.initials: S
authors.lastname: Feng
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Li
authors.forename: Yonggui
authors.initials: Y
authors.lastname: Fu
authors.forename: Peiran
authors.initials: P
authors.lastname: Yin
authors.forename: Zhen
authors.initials: Z
authors.lastname: Ai
authors.forename: Wenting
authors.initials: W
authors.lastname: Liu
authors.forename: Xueqing
authors.initials: X
authors.lastname: Yu
authors.forename: Ming
authors.initials: M
authors.lastname: Li
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005922:Glomerulonephritis, IGA / Q000453:epidemiology / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D005810:Multigene Family; D020641:Polymorphism, Single Nucleotide; D023084:alpha-Defensins / Q000235:genetics*
chemical_list: D023084:alpha-Defensins