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Multicenter Study
. 2010 Jun;5(6):1072-8.
doi: 10.2215/CJN.06550909. Epub 2010 Mar 18.

Examination of association with candidate genes for diabetic nephropathy in a Mexican American population

Sulgi Kim  1 , Hanna E Abboud, Madeleine V Pahl, John Tayek, Susan Snyder, James Tamkin, Harry Alcorn Jr, Eli Ipp, Cynthia C Nast, Robert C Elston, Sudha K Iyengar, Sharon G Adler
Affiliations
Multicenter Study

Examination of association with candidate genes for diabetic nephropathy in a Mexican American population

Sulgi Kim et al. Clin J Am Soc Nephrol. 2010 Jun.

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 x 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.

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Figures

Figure 1.
Figure 1.
Association test results for CNDP1 with (B) covariate configuration. Results for the two-marker tests are plotted on the midpoint of the two markers. Bonferroni corrected significance level of α = 0.05/42 is shown on the horizontal line.
Figure 2.
Figure 2.
Association test results for ELMO1 with (B) covariate configuration. Results for the two-marker tests are plotted on the midpoint of the two markers. Bonferroni corrected significance level of α = 0.05/227 is shown on the horizontal line.
Figure 3.
Figure 3.
Results for the eight other candidate genes. Significance levels of α = 0.05/401 are shown as horizontal lines.
Figure 4.
Figure 4.
Association test results for HMCN1 with (B) covariate configuration.
See this image and copyright information in PMC

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