Wu Changwei, Li Guisen, Wang Li
Renal Department and Nephrology Institute, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China.
Oncotarget. 2017 Aug 23;8(44):76492-76497. doi: 10.18632/oncotarget.20401. eCollection 2017 Sep 29.
Immunoglobulin A nephropathy (IgAN), the most common form of primary glomerular diseases worldwide, is a complex multifactorial disease. Previous genome wide association studies (GWAS) reported that variants CARD9 and VAV3 genes were associated with immunoregulation and susceptibility to IgAN. In this study, we further validated the associations and explored the interaction effect of rs4077515 and rs17019602 in IgAN patients.
There was no significant correlation between the two variants and IgAN ( > 0.05). The gene-gene analysis showed that rs4077515 and rs17019602 had interaction effect on the susceptibility to IgAN. For additive interaction, the CT or TT of rs4077515 and GG of 17019602 genotype combination conferred a 2.56-fold risk of IgAN reference to CC of 4077515 and AA of 17019602 (OR = 2.56, 95% CI: 0.98-6.69, = 0.049). In our study, clinical data was available for 543 patients. In comparison, neither rs4077515 nor rs17019602 showed significant association between genotype distribution and clinical parameters in IgAN patients ( > 0.05).
The case-control study included 586 patients with IgAN and 606 healthy controls. Variant rs4077515 of CARD9 gene and rs17019602 of VAV3 gene were genotyped by the ABI TaqMan probe assay.
The interaction effect of the variants of CARD9 and VAV3 genes increases the susceptibility to IgAN.
免疫球蛋白A肾病（IgAN）是全球原发性肾小球疾病最常见的形式，是一种复杂的多因素疾病。既往全基因组关联研究（GWAS）报道，CARD9和VAV3基因变异与免疫调节及IgAN易感性相关。在本研究中，我们进一步验证了这些关联，并探讨了rs4077515和rs17019602在IgAN患者中的相互作用效应。
这两个变异与IgAN之间无显著相关性（>0.05）。基因-基因分析显示，rs4077515和rs17019602对IgAN易感性有相互作用效应。对于加性相互作用，rs4077515的CT或TT与17019602基因型组合的GG相较于4077515的CC和17019602的AA，IgAN风险增加2.56倍（OR = 2.56，95%CI：0.98 - 6.69，P = 0.049）。在我们的研究中，543例患者有临床数据。相比之下，rs4077515和rs17019602在IgAN患者的基因型分布与临床参数之间均未显示出显著相关性（>0.05）。
病例对照研究纳入586例IgAN患者和606例健康对照。采用ABI TaqMan探针法对CARD9基因的rs4077515变异和VAV3基因的rs17019602进行基因分型。
CARD9和VAV3基因变异的相互作用效应增加了IgAN易感性。
