The NRF2 gene variant,-653G/A, is associated with nephritis in childhood-onset systemic lupus erythematosus
The NRF2 gene variant,-653G/A, is associated with nephritis in childhood-onset systemic lupus erythematosus
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DOI：
10.1177/0961203310367917
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发表时间：
2010-09-01
期刊：
影响因子：
2.6
通讯作者：
Orozco, L.
中科院分区：
文献类型：
--
作者：
Cordova, E. J.;Velazquez-Cruz, R.;Orozco, L.
系统性红斑狼疮（SLE）是一种与氧化应激相关的自身免疫性疾病，以慢性炎症为特征。肾功能不全是该病的侵袭性特征，但并非所有患者都存在肾功能不全。Nrf2-Keap1通路在抗氧化应激和炎症中起重要作用。小鼠模型和全基因组扫描表明NRF2（核因子（红细胞衍生2）样2）是SLE易感性的候选基因。因此，我们研究了NRF2多态性是否与墨西哥混血儿人群的儿童期SLE相关。采用TaqMan (R)方法对362例儿童期SLE患者和379例对照患者进行了2个单核苷酸多态性（snp）基因分型。我们发现在SLE易感性和NRF2多态性之间没有明显的关联。然而，在按性别进行人群分层后，-653G/A SNP的杂合基因型仅与女性肾炎显著相关[OR 1.81, CI (1.04-3.12), p = 0.032]。这种关联在患有严重肾炎的女性中更强[IV-VI级；OR = 2.16, CI (1.12-4.15), p = 0.019]。我们的研究结果表明NRF2与儿童期SLE的易感性无关，但它可能会给SLE患者带来肾功能衰竭的风险。狼疮（2010）19,1237-1242。
Systemic lupus erythematosus (SLE) is an autoimmune disease associated with oxidative stress and characterized by chronic inflammation. Kidney malfunction, an aggressive characteristic of this disease, is not present in all affected individuals. The Nrf2-Keap1 pathway is important in protecting against oxidative stress and inflammation. Mouse models and genome-wide scans have suggested NRF2 (Nuclear factor (erythroid-derived 2)-like 2) as a candidate gene for susceptibility to SLE. We therefore investigated whether NRF2 polymorphisms are associated with childhood-onset SLE in a Mexican Mestizo population. Two single nucleotide polymorphisms (SNPs) were genotyped by TaqMan (R) assays in 362 patients with childhood-onset SLE and 379 controls. We found no significant association between susceptibility to SLE and NRF2 polymorphisms. However, after population stratification by gender, the heterozygous genotype of the -653G/A SNP was significantly associated with nephritis in females only [OR 1.81, CI (1.04-3.12), p = 0.032]. This association was stronger in females affected with severe nephritis [classes IV-VI; OR = 2.16, CI (1.12-4.15), p = 0.019]. Our results suggest that NRF2 is not associated with susceptibility to childhood-onset SLE, but it could confer a risk for developing kidney malfunction in SLE-affected individuals. Lupus (2010) 19, 1237-1242.