Habieb Mona S, Dawood Ashraf A, Emara Mahmoud M, Elhelbawy Mohammad G, Elhelbawy Nesreen G
Medical Biochemistry & Molecular Biology Department, Faculty of Medicine, Menoufia University, Shebin Elkom City, Egypt.
Internal Medicine Department, Faculty of Medicine, Menoufia University, Shebin Elkom City, Egypt.
Appl Clin Genet. 2020 Nov 19;13:165-178. doi: 10.2147/TACG.S281502. eCollection 2020.
Diabetic nephropathy (DN), the primary driver of end-stage kidney disease, is a problem with serious consequences for society's health. Single nucleotide polymorphisms (SNPs) can define differences in susceptibility to DN and aid in development of personalized treatment. Giving the importance of epoxyeicosatrienoic acids (EETs) in kidney health, we aimed to study the association between two SNPs in the genes controlling synthesis and degradation of EETs rs2280275 and rs751141 respectively) and susceptibility of type 2 diabetes mellitus (T2DM) patients to develop DN.
Two hundred subjects were enrolled and categorized into three groups: group I (80 T2DM patients with DN), group II (60 T2DM patients without DN) and group III (60 healthy controls). Urea, creatinine, albumin/creatinine ratio (ACR), and eGFR were measured for all participants. Genotyping of rs2280275 and rs751141 was done by real time PCR.
There was no significant difference between the studied groups regarding rs2280275. In contrast, rs751141 was associated with increased risk of DN under a dominant model (GG vs GA+AA: OR=0.375; 95% CI (0.19-0.75), P=0.006) in unadjusted model and after adjustment for age and sex (OR=0.440; 95% CI (0.21-0.92), P=0.029), recessive model (AA vs GG+GA: OR=0.195; 95% CI (0.05-0.74), P=0.017) and additive model (GA vs GG+AA): OR=0.195; 95% CI (0.05-0.74), P=0.017).
rs2280275 was not associated with DN predisposition. However, rs751141 could be a genetic marker for development and progression of DN among Egyptian T2DM patients.
糖尿病肾病(DN)是终末期肾病的主要驱动因素,是一个对社会健康有严重后果的问题。单核苷酸多态性(SNP)可以确定对DN易感性的差异,并有助于个性化治疗的发展。鉴于环氧二十碳三烯酸(EETs)在肾脏健康中的重要性,我们旨在研究分别控制EETs合成和降解的基因中的两个SNP(rs2280275和rs751141)与2型糖尿病(T2DM)患者发生DN易感性之间的关联。
招募200名受试者并分为三组:第一组(80名患有DN的T2DM患者),第二组(60名无DN的T2DM患者)和第三组(60名健康对照)。对所有参与者测量尿素、肌酐、白蛋白/肌酐比值(ACR)和估算肾小球滤过率(eGFR)。通过实时PCR对rs2280275和rs751141进行基因分型。
在rs2280275方面,研究组之间无显著差异。相比之下,在未调整模型以及调整年龄和性别后,rs751141在显性模型(GG与GA + AA相比:OR = 0.375;95%CI(0.19 - 0.75),P = 0.006)中与DN风险增加相关(OR = 0.440;95%CI(0.21 - 0.92),P = 0.029),隐性模型(AA与GG + GA相比:OR = 0.195;95%CI(0.05 - 0.74),P = 0.017)和加性模型(GA与GG + AA相比):OR = 0.195;95%CI(0.05 - 0.74),P = 0.017)。
rs2280275与DN易感性无关。然而,rs751141可能是埃及T2DM患者中DN发生和进展的遗传标志物。