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Diabetes 53:486-491, 2004
© 2004 by the American Diabetes Association, Inc.

Examination of Candidate Chromosomal Regions for Type 2 Diabetes Reveals a Susceptibility Locus on Human Chromosome 8p23.1

Marcus G. Pezzolesi1, Moonsuk Nam1,2,4, Terumasa Nagase1,2, Tomasz Klupa1,2, Jonathon S. Dunn1, Wojciech M. Mlynarski1,2, Stephen S. Rich3, James H. Warram1, and Andrzej S. Krolewski1,2

1 Section on Genetics and Epidemiology, Joslin Diabetes Center, Boston, Massachusetts
2 Department of Medicine, Harvard Medical School, Boston, Massachusetts
3 Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina
4 Department of Internal Medicine, College of Medicine, Inha University, Incheon, Republic of Korea

In a panel of large Caucasian pedigrees, we genotyped markers in eight chromosomal regions previously reported as supporting linkage with type 2 diabetes. We previously reported significant linkage on chromosome 20q (maximum logarithm of odds score [MLS] = 2.79) in this panel. In the present analysis, candidate regions on 1q, 2q, 3q, 5q, 9q, and 10q yielded little evidence for linkage; a region on 2p (MLS = 1.64, P = 0.01 at position 9.0 cM) gave suggestive evidence of linkage; and a region on 8p (MLS = 3.67, P = 2.8 x 10-5, at position 7.6 cM) gave significant evidence of linkage. Conditional analyses were performed for both 2p and 8p regions and the region reported on 20q. The MLS for 2p increased from 1.64 to 1.79 (empirical P = 0.142) when conditioned for heterogeneity on 20q. The case was similar for 8p, where the MLS increased from 3.67 to 4.51 (empirical P = 0.023) when conditioned on families without evidence of linkage at 20q. In conclusion, our data support a type 2 diabetes susceptibility locus on chromosome 8p that appears to be independent from other susceptibility loci. Although we were able to replicate linkage in our pedigrees on chromosome 2p, we did not find evidence of linkage for regions on 1q, 2q, 3q, 5q, 9q, or 10q.

Address correspondence and reprint requests to Andrzej S. Krolewski, MD, PhD, Section on Genetics and Epidemiology, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215. E-mail: andrzej.krolewski{at}joslin.harvard.edu


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Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2004 by the American Diabetes Association.