Moussa Amira, Mabrouk Sameh, Hamdouni Haithem, Ajmi Maroua, Tfifha Miniar, Omezzine Asma, Abroug Saoussen, Bouslama Ali
Clin Lab. 2017 Jul 1;63(7):1233-1242. doi: 10.7754/Clin.Lab.2017.170203.
Oral steroid treatment is the first line of therapy for childhood nephrotic syndrome (NS). However, resistance to this treatment has been observed in some patients. Here, we investigated the association of two steroid metabolism-related genes with susceptibility to childhood NS and the steroid response.
We genotyped the single nucleotide polymorphisms (SNP) of MDR-1 [C1236T (rs1128503), G2677T/A (rs2032582), and C3435T (rs1045642)] and the CYP3A5 gene (A6986G) in 63 NS patients and 110 age and gender matched controls by PCR-RFLP.
Based on multivariate logistic regression analysis carrying the G2677A A allele seemed to multiply both the risk of NS and the risk of developing glucocorticoid (GC) resistance by three-fold (OR = 3.50, [1.37 - 7.06] , p < 0.001, OR = 3.07, [1.06 - 26.10], p = 0.048, respectively). When combined into haplotype, the TAT (1236_T, 2677_A, and 3435_T) haplotype conferred a two-fold NS risk (OR = 2.26, [1.11 - 4.58], p = 0.023) and almost three-fold risk to develop resistance to GC (OR = 2.69, [1.12 - 8.79], p = 0.044). However, TAT carriers seemed to have less risk to develop NS at late age (OR = 0.34, [0.12 - 0.92], p = 0.037). The C1236T (MDR-1) and the A6986G (CYP3A5) polymorphisms showed a trend of association to GC resistance but these associations did not reach the statistical significance (OR = 2.83, [0.54 - 14.67], p = 0.294), (OR = 2.11, [0.53 - 8.38], p = 0.28), respectively.
Here we report that only the G2677A polymorphism was associated to NS susceptibility and steroid resistance. The TAT haplotype was associated with NS susceptibility especially at an early age and with steroid resistance.
口服类固醇治疗是儿童肾病综合征（NS）的一线治疗方法。然而，在一些患者中已观察到对这种治疗的耐药性。在此，我们研究了两个类固醇代谢相关基因与儿童NS易感性及类固醇反应之间的关联。
我们通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对63例NS患者以及110例年龄和性别匹配的对照者的多药耐药蛋白1（MDR-1）基因的单核苷酸多态性（SNP）[C1236T（rs1128503）、G2677T/A（rs2032582）和C3435T（rs1045642）]和细胞色素P450 3A5（CYP3A5）基因（A6986G）进行基因分型。
基于多因素逻辑回归分析，携带G2677A A等位基因似乎使NS风险和发生糖皮质激素（GC）耐药的风险均增加了两倍（OR分别为3.50，[1.37 - 7.06]，p < 0.001；OR为3.07，[1.06 - 26.10]，p = 0.048）。当组合成单倍型时，TAT（1236_T、2677_A和3435_T）单倍型使NS风险增加了一倍（OR = 2.26，[1.11 - 4.58]，p = 0.023），并使发生GC耐药的风险增加了近两倍（OR = 2.69，[1.12 - 8.79]，p = 0.044）。然而，TAT携带者在晚年发生NS的风险似乎较低（OR = 0.34，[0.12 - 0.92]，p = 0.037）。C1236T（MDR-1）和A6986G（CYP3A5）多态性与GC耐药呈关联趋势，但这些关联未达到统计学意义（OR分别为2.83，[0.54 - 14.67]，p = 0.294；OR为2.11，[0.53 - 8.38]，p = 0.28）。
在此我们报告，只有G2677A多态性与NS易感性和类固醇耐药相关。TAT单倍型与NS易感性相关，尤其是在早年，并且与类固醇耐药相关。
