Han Shi-Sheng, Xu Yan-Qiu, Lu Yan, Gu Xiang-Chen, Wang Yi
Department of Nephrology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Medicine (Baltimore). 2017 Jun;96(24):e7191. doi: 10.1097/MD.0000000000007191.
Studies have investigated rs1128503, rs1045642, and rs2032582 in multidrug resistance protein 1 (MDR1) for association with susceptibility to idiopathic nephrotic syndrome (INS) and steroid resistance. However, because these findings were inconsistent, we performed a meta-analysis to determine whether there was evidence of a role of these MDR1 variants in INS.
The PubMed, Embase, and Web of Science databases were systematically searched to identify studies that examined MDR1 polymorphisms with susceptibility to INS and/or to steroid resistance. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by a fixed-effects or random-effects model based on heterogeneity.
We selected 9 case-control studies that included 928 patients with INS, of which steroid resistance data were available for 724 (236 were steroid resistant and 488 were steroid sensitive), and 879 healthy controls. All subjects were children. No significant relationships between these polymorphisms and INS susceptibility were identified. Significantly increased risk of steroid resistance was observed with rs1128503 allelic (OR = 1.49, 95% CI = 1.20-1.86) and genotypic (OR = 1.97, 95% CI = 1.18-3.30; OR = 2.03, 95% CI = 1.43-2.88) comparisons, and with allelic (OR = 1.56, 95% CI = 1.05-2.31) and genotypic (OR = 2.85, 95% CI = 1.15-7.07; OR = 2.21, 95% CI = 1.01-4.8) comparisons to rs2032582 in Caucasian populations. However, this association between rs2032582 and steroid resistance was not robust enough to withstand corrections for multiple comparisons. Similarly, we found that the rs1128503T-rs2032582G-rs1045642C (T-G-C) haplotype was associated with an increased risk of steroid resistance (OR = 2.02, 95% CI = 1.13-3.59), while the wild-type C-G-C haplotype was associated with a decreased risk (OR = 0.32, 95% CI = 0.12-0.88) in Caucasians; however, these findings were not significant following adjustments for multiple comparisons.
MDR1 rs1128503, rs1045642, and rs2032582 polymorphisms are not associated with INS susceptibility; however, there is evidence of an association between rs1128503 and increased risk of steroid resistance in children with INS, which indicates MDR1 may play a role in steroid resistance found in children with INS.
已有研究调查多药耐药蛋白1（MDR1）中的rs1128503、rs1045642和rs2032582与特发性肾病综合征（INS）易感性及激素抵抗的相关性。然而，由于这些研究结果不一致，我们进行了一项荟萃分析，以确定这些MDR1变异体在INS中是否发挥作用。
系统检索PubMed、Embase和Web of Science数据库，以识别研究MDR1基因多态性与INS易感性和/或激素抵抗的研究。根据异质性，采用固定效应或随机效应模型计算合并比值比（OR）和95%置信区间（CI）。
我们选择了9项病例对照研究，其中包括928例INS患者，其中724例有激素抵抗数据（236例激素抵抗，488例激素敏感），以及879例健康对照。所有受试者均为儿童。未发现这些基因多态性与INS易感性之间存在显著关系。在白种人群中，rs1128503等位基因（OR = 1.49，95%CI = 1.20 - 1.86）和基因型（OR = 1.97，95%CI = 1.18 - 3.30；OR = 2.03，95%CI = 1.43 - 2.�8）比较，以及与rs2032582的等位基因（OR = 1.56，95%CI = 1.05 - 2.31）和基因型（OR = 2.85，95%CI = 1.15 - 7.07；OR = 2.21，95%CI = 1.01 - 4.8）比较中，观察到激素抵抗风险显著增加。然而，rs2032582与激素抵抗之间的这种关联不够稳健，无法承受多重比较校正。同样，我们发现rs1128503T - rs2032582G - rs1045642C（T - G - C）单倍型与白种人激素抵抗风险增加相关（OR = 2.02，95%CI = 1.13 - 3.59），而野生型C - G - C单倍型与风险降低相关（OR = 0.32，95%CI = 0.12 - 0.88）；然而，在多重比较校正后，这些结果并不显著。
MDR1 rs1128503、rs1045642和rs2032582基因多态性与INS易感性无关；然而，有证据表明rs1128503与INS患儿激素抵抗风险增加有关，这表明MDR1可能在INS患儿的激素抵抗中起作用。
