Osman Wael M, Jelinek Herbert F, Tay Guan K, Khandoker Ahsan H, Khalaf Kinda, Almahmeed Wael, Hassan Mohamed H, Alsafar Habiba S
Center of Biotechnology, Khalifa University, Abu Dhabi, United Arab Emirates.
School of Community Health, Charles Sturt University, Albury, New South Wales, Australia.
BMJ Open. 2018 Dec 14;8(12):e020759. doi: 10.1136/bmjopen-2017-020759.
Within the Emirati population, risk factors and genetic predisposition to diabetic kidney disease (DKD) have not yet been investigated. The aim of this research was to determine potential clinical, laboratory and reported genetic loci as risk factors for DKD.
Four hundred and ninety unrelated Emirati nationals with type 2 diabetes mellitus (T2DM) were recruited with and without DKD, and clinical and laboratory data were obtained. Following adjustments for possible confounders, a logistic regression model was developed to test the associations of 63 single nucleotide polymorphisms (SNPs) in 43 genetic loci with DKD (145 patients with DKD and 265 without DKD). Linear regression models, adjusted for age and gender, were then used to study the genetic associations of five renal function traits, including 83 SNPs with albumin-to-creatinine ratio, 92 SNPs with vitamin D (25-OH cholecalciferol), 288 SNPs with estimated glomerular filtration rate (eGFR), 363 SNPs with serum creatinine and 73 SNPs with blood urea.
Patients with DKD, as compared with those without the disease, were mostly men (52%vs38% for controls), older (67vs59 years) and had significant rates of hypertension and dyslipidaemia. Furthermore, patients with DKD had T2DM for a longer duration of time (16vs10 years), which in an additive manner was the single factor that significantly contributed to the development of DKD (p=0.02, OR=3.12, 95% CI 1.21 to 8.02). Among the replicated associations of the genetic loci with different renal function traits, the most notable included with levels of serum creatinine, eGFR and DKD (P=0.04, OR=1.46); , and with vitamin D levels; as well as with serum creatinine and eGFR levels.
Associations were found between several genetic loci and risk markers for DKD, which may influence kidney function traits and DKD in a population of Arab ancestry.
在阿联酋人群中，尚未对糖尿病肾病（DKD）的危险因素和遗传易感性进行研究。本研究的目的是确定潜在的临床、实验室指标以及已报道的基因位点作为DKD的危险因素。
招募了490名患有和未患有DKD的2型糖尿病（T2DM）阿联酋无血缘关系的国民，并获取了临床和实验室数据。在对可能的混杂因素进行调整后，建立了逻辑回归模型，以检验43个基因位点中的63个单核苷酸多态性（SNP）与DKD的关联（145例DKD患者和265例非DKD患者）。然后使用针对年龄和性别进行调整的线性回归模型，研究五个肾功能性状的遗传关联，包括83个与白蛋白肌酐比值相关的SNP、92个与维生素D（25-羟基胆钙化醇）相关的SNP、288个与估算肾小球滤过率（eGFR）相关的SNP、363个与血清肌酐相关的SNP以及73个与血尿素相关的SNP。
与未患DKD的患者相比，DKD患者男性居多（52%对对照组的38%），年龄更大（67岁对59岁），高血压和血脂异常发生率显著更高。此外，DKD患者患T2DM的时间更长（16年对10年），这以累加方式是导致DKD发生的单一显著因素（p=0.02，OR=3.12，95%CI 1.21至8.02）。在基因位点与不同肾功能性状的重复关联中，最显著的包括与血清肌酐水平、eGFR和DKD的关联（P=0.04，OR=1.46）；与维生素D水平的关联；以及与血清肌酐和eGFR水平的关联。
在几个基因位点与DKD的风险标志物之间发现了关联，这可能会影响阿拉伯血统人群的肾功能性状和DKD。
