Examination of Association with Candidate Genes for... : Clinical Journal of the American Society of Nephrology (original) (raw)

Original Articles: Original Articles

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

Kim, Sulgi*; Abboud, Hanna E.†; Pahl, Madeleine V.‡; Tayek, John§; Snyder, Susan§; Tamkin, James‖; Alcorn, Harry Jr.¶; Ipp, Eli§; Nast, Cynthia C.§; Elston, Robert C.*; Iyengar, Sudha K.*; Adler, Sharon G.§

*Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio;

†Department of Medicine, University of Texas, Austin, Texas;

‡Division of Nephrology and Hypertension, University of California–Irvine, Irvine, California;

§Los Angeles Biomedical Research Institute at Harbor–UCLA Medical Center, Torrance, California;

‖Providence Medical Institute, Torrance, California; and

¶DaVita Clinical Research, Minneapolis, Minnesota

Correspondence: Dr. Sharon G. Adler, Harbor-UCLA Medical Center, Division of Nephrology and Hypertension, 1124 West Carson Street, Torrance, CA 90509. Phone: 310-222-3891; Fax: 310-782-1837; E-mail: [email protected]

S.K.I. and S.G.A. contributed equally to this work.

Received September 15, 2009

Accepted February 10, 2010

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 = 6.1 × 10−5). Association with a rare haplotype in this region was subsequently identified.

Conclusions: 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.