Examination of Association with Candidate Genes for Diabetic Nephropathy in a Mexican American Population

Abstract

Background and objectives: Diabetic nephropathy (DN) is a multifactorial complication characterized by persistent proteinuria in susceptible individuals with type 1 and type 2 diabetes. Disease burden in people of Mexican-American descent is particularly high, but there are only a few studies that characterize genes for DN in this ethnic group. Two genes, carnosine dipeptidase 1 (CNDP1) and engulfment and cell motility 1 (ELMO1) previously showed association with DN in other ethnic groups. CNDP1 and ELMO1 were examined along with eight other genes that are less well characterized for DN in a new study of Mexican-Americans.Design, setting, participants, & measurements: The target sample was patients of Mexican-American ancestry collected from three centers: 455 patients with DN and 437 controls with long-term diabetes but no incident nephropathy. Forty-two, 227, and 401 single nucleotide polymorphisms (SNPs) in CNDP1, ELMO1, and the other eight genes, respectively, were examined.Results: No region in CNDP1 or ELMO1 showed significant P values. Of the other eight candidate genes, an association of DN with a SNP pair, rs2146098 and rs6659783, was found in hemicentin 1 (HMCN1) (unadjusted P ‫؍‬ 6

Association of rs11643718SLC12A3and rs741301ELMO1Variants with Diabetic Nephropathy in South Indian Population

“…The significant association of the ELMO1 (engulfment and cell motility 1) rs741301 (Int18+9170 A/G) variant with type 2 diabetic nephropathy found in the present study is similar to that reported in Japanese (Shimazaki et al., ) and Chinese population (Wu et al., ) and in contradiction to that reported in Mexican Americans (Kim et al., ) and north Indians (Yadav et al., ). Though the association of rs741301 SNP with DN was not replicated in American Indian(Hanson et al., ) and African American population (Leak et al., ), other SNPs in intron 13 of the ELMO1 gene were found to be associated with nephropathy in those studies confirming the candidature of ELMO1 gene in the susceptibility to nephropathy.…”

Common variants in CNDP1 and CNDP2, and risk of nephropathy in type 2 diabetes

“…In a follow-up study in African-Americans the same team identified two single nucleotide polymorphism (SNPs) in CNDP1 and CNDP2 that were associated with type 2 diabetes and ESRD [17]. However, several studies have not been able to replicate these findings [18,19], nor has any association been shown between the CNDP locus and diabetic nephropathy in type 1 diabetes [20][21][22]. The 5L-5L genotype of the D18S880 marker has been reported to be associated with low serum CNDP concentrations in diabetic patients [15], making the CNDP genes interesting candidates for diabetic nephropathy susceptibility.…”

High Elmo1 expression aggravates and low Elmo1 expression prevents diabetic nephropathy

“…In a genome-wide case control association study in Japan, over 80,000 single-nucleotide polymorphism (SNP) loci were tested and one SNP locus in the 18th intron of the ELMO1 gene was found to be strongly associated with nephropathy due to type 2 diabetes (χ 2 = 19.9; P = 0.000008; odds ratio, 2.7) (5). Later studies have demonstrated an association of SNPs in the ELMO1 gene and the susceptibility to type 1 diabetic nephropathy in Caucasians (6,7), Pima Indians (8), African Americans (9), and Chinese population (10), although some other studies have reported that the association is not significant (11,12).…”