Association of ELMO1 gene polymorphism and diabetic nephropathy among Egyptian patients with type 2 diabetes mellitus

Abstract

Background and ObjectiveDiabetic nephropathy (DN) is the most common cause of end stage renal failure or even death among patients with type 2 diabetes mellitus. Genetic predisposition is widely studied among these patients to identify manageable aspects of the disease pathogenesis. This study was carried out to test the association of engulfment and cell motility 1 (ELMO1) gene polymorphism with DN among Egyptians. ELMO1 is required for phagocytosis of apoptotic cells and cell motility.MethodsThis case‐control study was conducted on type 2 diabetic patients who attended Suez Canal University Hospital, Egypt, between November 2016 and October 2017. Peripheral blood was collected from 200 diabetic patients (without nephropathy), 200 patients with DN, and 100 healthy controls for DNA extraction. The single nucleotide polymorphism of ELMO1 (rs741301) was genotyped using real‐time polymerase chain reaction and the allele discrimination technique.ResultsGG genotype was significantly associated with DN (odds ratio [OR] = 2.7; 95% confidence interval [CI]: 1.4‐5.3) (P = .016). The OR for the high‐risk allele (G) was 1.9 with 95% CI from 1.5 to 2.9 (P < .001).ConclusionELMO1 gene (rs741301) polymorphism is a candidate variant in the predisposition to DN.

Role of engulfment and cell motility 1 (ELMO1) gene polymorphism in development of diabetic kidney disease

“…Bodhini et al [38] found that the frequency of the G allele of ELMO1 rs741301 variant was relatively higher in the DM patients than in DKD patients, indicating that the A allele is the nonrisk allele and the G allele is the risk allele. These findings were not in line with those of Bayoumy et al [29], who observed that ELMO1 rs741301 A>G was a candidate variant in genetic predisposition to DKD. GG genotype was substantially correlated with DKD (OR = 2.7, 95% CI 1.4-5.3, p = 0.016).…”

“…Compared to the control group, the patient groups had higher blood pressure, serum creatinine, and ACR and lower eGFR. This result is in line with that of Bayoumy et al [29], who found a significant difference in these variables between patients and controls. Patient groups have high FBG and 2-hPPG (p < 0.001), while HbA1c was significantly elevated in group 1 (p < 0.001).…”

“…Chandra et al [28] also, observed no significant difference in BMI and WHR between DKD and non-DKD. Disease duration was significantly longer in group 1 than group 2, in agreement with the findings of Wu et al and Bayoumy et al [16,29], who found a significant relationship between disease duration and DKD. Long duration of diabetes had a significant effect on kidney functions and electrolytes levels and is considered a risk factor for DKD.…”

Single-nucleotide polymorphisms as important risk factors of diabetes among Middle East population

“…DN patients with GG genotype and G allele were more than twice as likely to develop DN. The ELMO1 (rs741301) polymorphism increased the DN susceptibility among T2D patients [ 343 ]. SNARE protein family including VAMP2 and SNAP25 are structural proteins involved in insulin secretion through the vesicle fusion.…”

Functional Verification of Novel ELMO1 Variants by Live Imaging in Zebrafish

“…DOCK2 deficiency has been reported to be associated with immunodeficiency diseases (Dobbs et al, 2015). Conversely, analyses of genetic polymorphisms in different human populations around the world found that ELMO1 was associated with autoimmune diseases such as diabetes, rheumatoid arthritis, and nephropathy, but not immunodeficiency diseases (Hironori Katoh, 2006;Arandjelovic et al, 2019;Bayoumy et al, 2020). In addition to DOCK2, ELMO1 also interacts with DOCK180 to regulate cell migration (Grimsley et al, 2004).…”