Association of single nucleotide polymorphism (rs741301) of the ELMO1 gene with diabetic kidney disease in Polish patients with type 2 diabetes: a pilot study

Abstract

Introduction: Multifactorial pathogenesis of diabetic kidney disease (DKD) consists of a combination of metabolic, environmental, and genetic factors. A genome-wide association study has shown that ELMO1 is a candidate gene for DKD occurrence and progression. The aim of this study was to assess the association of a single nucleotide polymorphism (rs741301) of the ELMO1 gene with DKD in Polish patients with type 2 diabetes (T2DM). Material and methods: This was a case/control study of 272 T2DM patients with or without DKD. Patients were divided into groups depending on DKD definition according to the American Diabetes Association (ADA) and the National Kidney Foundation (NKF). The association of the rs741301 polymorphism with DKD was assessed in the whole study group as well as in the subgroups stratified according to the presence of DKD. Results: There was no association between rs741301 polymorphisms and the presence of DKD in relation to the ADA definition (p = 0.6) or the NKF definition (p = 0.5) of DKD and with estimated glomelural filtration rate (eGFR) value reflecting the stage of the chronic kidney disease (p = 0.8). Conclusions: Even though the results of this study are negative, there is still a great need for larger studies assessing the genetic susceptibility to DKD to identify patients who are particularly prone to this complication.

Association between ELMO1 gene polymorphisms and diabetic kidney disease: A systematic review and meta-analysis

“…This systematic review finally included 17 studies, of which 15 studies were eligible and included in meta-analysis and the other two studies were excluded due to lack of data (Fig 1). Twelve studies followed a case-control design [4,11,[25][26][27][28][29][30][31][32][33][34] while the other 5 were genomewide association studies [7,[35][36][37][38], with a total of 5794 DM with DKD patients, 4886 DM without DKD patients, and 2023 healthy controls to assess the impact of ELMO1 polymorphism on DKD susceptibility. Most studies included patients with T2DM, except for two studies with T1DM patients [7,36].…”

“…Studies were sub-grouped based on their geographical region; Middle East [25,28,29,32,37], South Asia [26,31,33,35], East Asia [4,11,30,33,38], Europe [34], and USA [7,27,36].…”

“…For example, for EMLO1 rs741301 polymorphism under the allele model in DKD vs. DM patients, the test for subgroup differences suggests that there is a statistically significant subgroup effect (p = 0.00) and no heterogeneity was observed in Middle East (I 2 = 0%). However due to the unknown pathogenesis of DKD, studies which caused this heterogeneity [34,35] were unable to specifically justify the disagreements of their findings with other studies; thus resorting to general statements such as genetic and environmental factors, racial differences, ethnic confounders, and small sample sizes.…”

Association of chemotactic cytokine receptor 5 (CCR5) gene polymorphism (59029 A/G, rs1799987) with diabetic kidney disease in patients with type 2 diabetes from Poland

“…lar to the one we used to examine the association of the ELMO1 (Engulfment and cell motility 1) gene and DKD in our previous study on a different group of patients with T2DM [24]. The inclusion criteria for the current study were as follows: T2DM and the presence (cases) or lack of DKD (controls).…”

What do we know about biomarkers in diabetic kidney disease?

“…for research is based on the pathophysiological reasons for the development of DKD [16]. However, the opposite scenario is possible -for example, genome-wide association studies (GWAS) [17,18] or proteomics studies identify genes or proteins significantly related to the occurrence of a given disease phenotype, and pathophysiological relationships between a given biomarker and development of the disease are unknown. Therefore, the search for biomarkers also broadens the knowledge of the pathophysiology of diseases, focusing the researchers' attention on explaining the relationship between the newly identified biomarker and the mechanism of disease development.…”