Suggestive Linkages Between Markers on Human 1p32‐p22 and Body Fat and Insulin Levels in the Québec Family Study

Abstract

A single‐gene rodent mutation (diabetes) and a quantitative trait locus (dietary obese 1) mapped to the mid portion of mouse chromosome 4 have been related to obesity and/or insulin levels. Synteny relationships place their putative human homologs on 1p31 and 1p35‐p31, respectively. In 137 sibships of adult brothers and sisters from the Québec Family Study, genetic linkages between seven microsatellite markers from 1p32‐p22 and various obesity‐ and diabetes‐related quantitative phenotypes were examined using single locus sibpair linkage analysis. Suggestive linkages were observed between markers D1S476 and body mass index (p>=Q.Q5), fat mass (p=0.02), the sum of six skinfolds (p=0.02), the insulin area after an oral glucose tolerance test (p=0.02), and between the neighboring marker D1S200 and body mass index (p>=0.03), and fat mass (p=0.009). Suggestive linkages were also observed between the more telomeric markers D1S193 and body mass index (p=0.03), and between the neighboring marker DIS 197 and fasting insulin level (p=0.05). No linkage was observed with the trunk to extremity skinfolds ratio. These linkages suggest that human homologs of the mouse diabetes or dietary obese 1 and/or other genes in this interval on chromosome 1 play a role in the regulation of body mass, body composition, and insulin levels, but not of subcutaneous fat distribution.