Pathogenesis of IgA nephropathy: advances in molecular genetics research

doi:10.3877/cma.j.issn.2095-3216.2014.02.003

Abstract

Abstract:

IgA nephropathy (IgAN) is a polygenic and multifactorial complex disease. Genetic factors are involved in the development and progression of IgAN. Two approaches have been applied in genetic studies of IgAN, including pedigree-based linkage studies and sporadic patients-based association studies. Although linkage analyses have yielded genetic signals at 6q22-23, 4q26-31, 17q12-22 and 2q36 for familial IgAN, no underlying gene in these loci has been identified. Early association studies were based on candidate genes. Peking University Institute of Kidney Diseases group' s previous candidate-gene association study showed for the first time an association of genetic variants in the genes encoding key enzymes of O-glycosylation of IgA1 with susceptibility to IgAN. Recently, genome-wide association studies(GWAS) have identified five susceptibility loci for IgAN, including the major histocompatibility complex(MHC) region implicated in adaptive immunity, the 8p23, 17p13 and 22q12 loci implicated in innate immunity, and the 1q32 locus implicated in complement regulation. The GWAS has brought us not only mass data, but lots of opportunities and challenges as well.

Key words: IgA nephropathy, Genetics, Linkage analysis, Association analysis

Li Zhu, Hong Zhang. Pathogenesis of IgA nephropathy: advances in molecular genetics research[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2014, 03(02): 68-72.

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References 35

1	D'Amico G. The commonest glomerulonephritis in the world: IgA nephropathy [J]. Q J Med,1987,64(245):709-727.
2	Barratt J, Feehally J. IgA nephropathy [J]. J Am Soc Nephrol,2005,16(7):2088-2097.
3	D'Amico G. Natural history of idiopathic IgA nephropathy and factors predictive of disease outcome [J]. Semin Nephrol,2004,24(3):179-196.
4	Kiryluk K, Julian BA, Wyatt RJ, et al. Genetic studies of IgA nephropathy: past, present, and future [J]. Pediatr Nephrol,2010,25(11):2257-2268.
5	Chang JH, Kim DK, Kim HW, et al. Changing prevalence of glomerular diseases in Korean adults: a review of 20 years of experience [J]. Nephrol Dial Transplant, 2009, 24(8): 2406-2410.
6	Kitajima T, Murakami M, Sakai O. Clinicopathological features in the Japanese patients with IgA nephropathy [J]. Jpn J Med,1983,22(3):219-222.
7	Zhou FD, Zhao MH, Zou WZ, et al. The changing spectrum of primary glomerular diseases within 15 years: a survey of 3331 patients in a single Chinese centre [J]. Nephrol Dial Transplant,2009,24(3):870-876.
8	Donadio JV, Grande JP. IgA nephropathy [J]. N Engl J Med,2002,347(10):738-748.
9	Smith SM, Tung KS. Incidence of IgA-related nephritides in American Indians in New Mexico [J]. Hum Pathol,1985,16(2):181-184.
10	Pontier PJ, Patel TG. Racial differences in the prevalence and presentation of glomerular disease in adults [J]. Clin Nephrol,1994,42(2):79-84.
11	Schena FP,Cerullo G,Rossini M,et al. Increased risk of end-stage renal disease in familial IgA nephropathy [J]. J Am Soc Nephrol,2002,13(2):453-460.
12	Tolkoff-Rubin NE, Cosimi AB, Fuller T, et al. IGA nephropathy in HLA-identical siblings [J]. Transplantation,1978,26(6):430-433.
13	Masuda J, Shiiki H, Fujii Y, et al. Identical twin sisters with IgA nephropathy [J]. Nippon Jinzo Gakkai Shi,1996,38(1):52-56.
14	Li PK, Burns AP, So AK, et al. Familial IgA nephropathy: a study of HLA class II allogenotypes in a Chinese kindred [J]. Am J Kidney Dis,1992,20(5):458-462.
15	Julian BA, Quiggins PA, Thompson JS, et al. Familial IgA nephropathy. Evidence of an inherited mechanism of disease [J]. N Engl J Med,1985,312(4):202-208.
16	吕继成, 张宏, 陈育青, 等. 家族性IgA 肾病-777 例中国IgA 肾病回顾性调查分析[J]. 中华肾脏病杂志,2004,20(1):5-7.
17	Gharavi AG, Yan Y, Scolari F, et al. IgA nephropathy, the most common cause of glomerulonephritis, is linked to 6q22-23 [J]. Nat Genet,2000,26(3):354-357.
18	Bisceglia L, Cerullo G,Forabosco P, et al. Genetic heterogeneity in Italian families with IgA nephropathy: suggestive linkage for two novel IgA nephropathy loci [J]. Am J Hum Genet,2006, 79(6):1130-1134.
19	Paterson AD, Liu XQ,Wang K,et al. Genome-wide linkage scan of a large family with IgA nephropathy localizes a novel susceptibility locus to chromosome 2q36 [J]. J Am Soc Nephrol,2007,18(8):2408-2415.
20	马序竹, 张宏, 王素霞, 等. IgA 肾病合并肾小球基底膜弥漫性变薄的临床特点及COL4A3/COL4A4 的基因连锁分析[J]. 中华肾脏病杂志,2006,22(5):261-265.
21	Li PK, Poon AS, Lai KN. Molecular genetics of MHC class Ⅱalleles in Chinese patients with IgA nephropathy [J]. Kidney Int,1994,46(1):185-190.
22	Deenitchina SS, Shinozaki M, Hirano T, et al. Association of a Tcell receptor constant alpha chain gene polymorphism with progression of IgA nephropathy in Japanese patients [J]. Am J Kidney Dis,1999,34(2):279-288.
23	Pei Y,Scholey J,Thai K,et al. Association of angiotensinogen gene T235 variant with progression of immunoglobin A nephropathy in Caucasian patients [J]. J Clin Invest,1997,100(4):814-820.
24	Syrjanen J, Hurme M, Lehtimaki T, et al. Polymorphism of the cytokine genes and IgA nephropathy [J]. Kidney Int, 2002, 61(3):1079-1085.
25	Takei T, Iida A, Nitta K, et al. Association between singlenucleotide polymorphisms in selectin genes and immunoglobulin A nephropathy [J]. Am J Hum Genet,2002,70(3):781-786.
26	Gharavi AG, Moldoveanu Z, Wyatt RJ, et al. Aberrant IgA1 glycosylation is inherited in familial and sporadic IgA nephropathy[J]. J Am Soc Nephrol,2008,19(5):1008-1014.
27	Lin X, Ding J, Zhu L, et al. Aberrant galactosylation of IgA1 is involved in the genetic susceptibility of Chinese patients with IgA nephropathy [J]. Nephrol Dial Transplant,2009,24(11):3372-3375.
28	Li GS, Zhang H, Lv JC, et al. Variants of C1GALT1 gene are associated with the genetic susceptibility to IgA nephropathy [J].Kidney Int,2007,71(5):448-453.
29	Li GS, Zhu L, Zhang H, et al. Variants of the ST6GALNAC2 promoter influence transcriptional activity and contribute to genetic susceptibility to IgA nephropathy [J]. Hum Mutat,2007,28(10):950-957.
30	Li GS, Nie GJ, Zhang H, et al. Do the mutations of C1GALT1C1 gene play important roles in the genetic susceptibility to Chinese IgA nephropathy [J] ? BMC Med Genet,2009,10:101.
31	Zhu L, Tang W, Li G, et al. Interaction between variants of two glycosyltransferase genes in IgA nephropathy [J]. Kidney Int,2009,76(2):190-198.
32	Feehally J, Farrall M, Boland A, et al. HLA has strongest association with IgA nephropathy in genome-wide analysis[J]. J Am Soc Nephrol,2010,21(10):1791-1797.
33	Gharavi AG, Kiryluk K, Choi M, et al. Genome-wide association study identifies susceptibility loci for IgA nephropathy [J]. Nature genetics,2011,43(4):321-327.
34	Yu XQ, Li M, Zhang H, et al. A genome-wide association study in Han Chinese identifies multiple susceptibility loci for IgA nephropathy [J]. Nature genetics,2012,44(2):178-182.
35	Kiryluk K, Li Y, Sanna-Cherchi S, et al. Geographic differences in genetic susceptibility to IgA nephropathy: GWAS replication study and geospatial risk analysis [J]. PLoS Genet, 2012, 8 (6):e1002765.

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