Interaction between ELMO1 gene polymorphisms and environment factors on susceptibility to diabetic nephropathy in Chinese Han population

Abstract

Background: The association of diabetic nephropathy (DN) risk with single nucleotide polymorphisms (SNPs) within Engulfment and Cell Motility 1 (ELMO1) gene and gene-environment synergistic effect have not been extensively examined in, therefore, the purpose of this study is to explore the association between multiple SNPs in ELMO1 gene, and the relationship between gene-environment synergy effect and the risk of DN. Methods: Genotyping for 4 SNPs was performed with polymerase chain reaction (PCR) and following restriction fragment length polymorphism (RFLP) methods. Hardy-Weinberg balance of the control group was tested by SNPstats (online software: http://bioin fo.icono logia .net/snpst ats). The best combination of four SNPs of ELMO1 gene and environmental factors was screened by GMDR model. Logistic regression was used to calculating the OR values between different genotypes of ELMO1 gene and DN. Results: The rs741301-G allele and the rs10255208-GG genotype were associated with an increased risk of DN risk, adjusted ORs (95% CI) were 1.75 (1.19-2.28) and 1.41 (1.06-1.92), respectively, both p-values were < 0.001. We also found that the others SNPs-rs1345365 and rs7782979 were not significantly associated with susceptibility to DN. GMDR model found a significant gene-alcohol drinking interaction combination (p = 0.0107), but no significant gene-hypertension interaction combinations. Alcohol drinkers with rs741301-AG/GG genotype also have the highest DN risk, compared to never drinkers with rs741301-AA genotype, OR (95% CI) 3.52 (1.93-4.98). Conclusions: The rs741301-G allele and the rs10255208-GG genotype, gene-environment interaction between rs741301 and alcohol drinking were all associated with increased DN risk.

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

“…Patient groups have high FBG and 2-hPPG (p < 0.001), while HbA1c was significantly elevated in group 1 (p < 0.001). These findings agreed with those of Mehrabzadeh et al and Hou et al [30,31], who observed that DKD had higher levels of HbA1c than T2DM without DKD. HbA1c is a good indicator of glycemic state.…”

“…The high-risk allele G had the following values: OR = 1.9, 95% CI 1.5-2.9, p < 0.001, suggesting that ELMO1 could be a valuable target for new drugs to aid in the prevention and treatment of DKD. Hou et al and Mohammed et al [31,39] confirmed that homozygous mutant GG genotype and G allele of rs741301 were significant risk predictors of predisposition to DKD in T2DM patients.…”

The UK Chinese population with kidney failure: Clinical characteristics, management and access to kidney transplantation using 20 years of UK Renal Registry and NHS Blood and Transplant data

“…The prevalence of diabetes in the UK Chinese was reported as 3.8% in men and 3.3% in women [ 21 ] in 2004, but may have increased subsequently, as has been reported in China [ 22 , 23 ] and Hong Kong [ 24 ], where prevalence of diabetes has risen and is reported as 11% and 10% respectively. Specific variations in RAGE [ 25 ], ELMO1 [ 26 ] and TGF-β1 [ 27 ] genes, and their gene-environment interactions, have been found to be associated with diabetic nephropathy in the Han Chinese population, but have not been investigated in the Chinese diaspora, where environmental exposures may be different. The Chinese Kidney Disease Network (CK-NET) has reported a 15.1% prevalence of glomerulonephritis in their CKD population, 10.6% of which were diagnosed with IgA nephropathy, a number which had fallen from 19% in 2010 [ 1 ], which is lower than the 54% prevalence of IgA nephropathy in patients with glomerulonephritis in this UK study.…”

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].…”

“…Most studies included patients with T2DM, except for two studies with T1DM patients [7,36]. India [5,8,10,15,26,31,33,35] and China [2,4,5,9,14,30,33,38] were countries with the most studies.…”