Abstract
Previous genome-wide association studies have discovered significant association at ITGAX-ITGAM on 16p11.2 for IgA nephropathy (IgAN). In this study, we performed a two-stage association study that enrolled 1700 IgAN cases and 2400 controls to further investigate the relationship of ITGAX and ITGAM gene polymorphisms with IgAN. Seven single-nucleotide polymorphisms (SNPs) were selected for genotyping in 1000 IgAN cases and 1000 healthy controls in the discovery stage, and the significant SNP was further validated in additional 700 IgAN cases and 1400 healthy controls. We found that four SNPs (rs11150619, rs11150614, rs7190997, and rs4597342) showed potential associations with IgAN susceptibility in the discovery stage, but only SNP rs11150619 was further genotyped in the validation stage after multiple testing. The results indicated that rs11150619 was significantly associated with IgAN in the combined samples (OR = 0.81, 95%CI = 0.71–0.91, and dominant P = 6.68 × 10−4). Moreover, patients with TT genotype of rs11150619 exhibited increased estimated glomerular filtration rate levels and a reduced proportion of global sclerosis compared with those with TC and CC genotypes. Our results suggested that ITGAX and ITGAM gene polymorphisms were associated with IgAN in a Chinese Han population, and the rs11150619-T allele showed a potential protective role for IgAN.
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Acknowledgements
This research was funded in part by the National Key Research and Development Project, China (No. 2016YFC0906101), the Operational Grant of Guangdong Provincial Key Laboratory, China (No. 2017B030314019), the Guangdong Provincial Program of Science and Technology, China (No. 2017A050503003; No. 2017B020227006), the National Natural Science Foundation of China (No. 81770661; No. 81570599; No. 81570750), the Guangzhou Municipal Program of Science and Technology, China (No. 2016201604030005; No. 201704020167; No. 201807010002) and the Young and Middle-aged Talents Program of The First Affiliated Hospital, Sun Yat-sen University.
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Shi, D., Zhong, Z., Xu, R. et al. Association of ITGAX and ITGAM gene polymorphisms with susceptibility to IgA nephropathy. J Hum Genet 64, 927–935 (2019). https://doi.org/10.1038/s10038-019-0632-2
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DOI: https://doi.org/10.1038/s10038-019-0632-2
