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

Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA.
Clinical Journal of the American Society of Nephrology (Impact Factor: 4.61). 03/2010; 5(6):1072-8. DOI: 10.2215/CJN.06550909
Source: PubMed


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.
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.
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 = 6.1 x 10(-5)). Association with a rare haplotype in this region was subsequently identified.
The associations in CNDP1 or ELMO1 were not replicable; however, an association of DN with HMCN1 was found. Additional work at this and other loci will enable refinement of the genetic hypotheses regarding DN in the Mexican-American population to find therapies for this debilitating disease.

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