Genetics and DevelopmentFamily-Based Association Study Showing that Immunoglobulin A Nephropathy Is Associated with the Polymorphisms 2093C and 2180T in the 3′ Untranslated Region of the Megsin GeneLi, You-Ji*; Du, Yong*; Li, Cai-Xia†; Guo, Hui‡; Leung, Joseph C.K.§; Lam, Man F.§; Yang, Niansheng*; Huang, Fengxian*; Chen, Yun‡; Fang, Ji-Qian†; Maxwell, Patrick H.¶; Lai, Kar N.§; Wang, Yiming‡ Author Information *Department of Nephrology, 1st Affiliated Hospital, †Department of Medical Statistics, and ‡Department of Medical Genetics, Zhongshan Medical College, Sun Yat-Sen University, Guangzhou, People’s Republic of China; §Department of Medicine, Queen Marry Hospital, The University of Hong Kong, Hong Kong; and ¶Department of Medicine, Hammersmith Hospital, Imperial College, London, United Kingdom. Correspondence to Prof. Yiming Wang, Dept of Medical Genetics, Zhongshan Medical College, 74 Zhongshan Road II, Guangzhou 510089, PR China. Phone: 86-20-87333136; Fax: 86-20-87335785; E-mail: [email protected] Accepted April 14, 2004 Received October 24, 2003 Journal of the American Society of Nephrology 15(7):p 1739-1743, July 2004. | DOI: 10.1097/01.ASN.0000130858.00688.46 Buy Metrics Abstract ABSTRACT. Immunoglobulin A nephropathy (IgAN) is considered to be a multifactorial disease with genetic and environmental factors contributing to its pathogenesis. The genes involved in susceptibility and progression of the disease have not yet been clearly elucidated. Megsin (SERPINB7) is an important candidate gene, predominantly expressed in glomerular mesangium and upregulated in IgAN. To investigate the potential role of this and other genes in IgAN, patients with biopsy-proven IgAN were recruited, as were family members, for a family-based association study. The genotypes of the polymorphisms C2093T and C2180T within the 3′ untranslated region of the gene were determined by polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. The results were analyzed by transmission disequilibrium test (TDT) and haplotype relative risk (HRR). TDT analyses revealed that Megsin 2093C and 2180T alleles were significantly more transmitted from heterozygous parents to patients than expected (C2093T: 127 trios, P = 0.034, C2180T: 100 trios, P = 0.002). Extended TDT showed increased cotransmission of the 2093C and 2180T alleles (232 families, P < 0.001). HRR revealed that the 2093C and 2180T alleles were more often transmitted to patients (P = 0.014, <0.001, respectively). Genetic variation in Megsin confers susceptibility to IgAN. Copyright © 2004 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.