A quantitative trait locus influencing fasting plasma glucose in chromosome region 18q22-23.

Fasting plasma glucose is a multigenic trait related to both diabetes and obesity. We performed a genome scan for quantitative fasting plasma glucose levels in 320 families (1,514 subjects), segregating extreme obesity and normal weight using 382 autosomal microsatellite markers. We found significant linkages on 18q22-23 using family regression (logarithm of odds [LOD] 3.67, P = 0.00002, D18S1371 at 116 cM) and variance components (LOD 4.48, P < 0.00001) methods. Evidence for linkage remained strong when restricted to European Americans (260 families, 1,258 individuals). After an additional 60 families were added, the linkage signal strengthened (LOD 6.59). The result on 18q22-23 remained significant, even after controlling for both BMI and diabetes status. We also found suggestive linkages on chromosomes 2 (LOD 1.58, 216 cM) and 7 (LOD 1.78, 163 cM). Our results suggest that there is a quantitative trait locus in chromosome region 18q22-23 that influences fasting glucose levels and may play a role in the pathogenesis of type 2 diabetes. The strength of the serum glucose results after controlling for BMI suggests that this putative gene does not influence glucose levels merely through an effect on obesity.

A genome scan for serum triglyceride in obese nuclear families.

Serum triglyceride (TG) levels are increased in extremely obese individuals, indicating abnormalities in lipid metabolism and insulin resistance. We carried out a genome scan for serum TG in 320 nuclear families segregating extreme obesity and normal weight. Three hundred eighty-two Marshfield microsatellite markers (Screening Set 11) were genotyped. Quantitative linkage analyses were performed using family regression and variance components methods. We found linkage on the 7q36 region [D7S3058, 174 centimorgan (cM), Logarithm of Odds (LOD) = 2.98] for log-transformed TG. We also found suggestive linkages on chromosomes 20 (D20S164, 101 cM, LOD = 2.34), 13 (111 cM, LOD = 2.00), and 9 (104 cM, LOD = 1.90) as well as some weaker trends for chromosomes 1, 3, 5, 10, 12, and 22. In 58 African American families, LOD scores of 3.66 and 2.62 were observed on two loci on chromosome 16: D16S3369 (64 cM) and MFD466 (100 cM). To verify the 7q36 linkage, we added 60 nuclear families, and the LOD score increased to 3.52 (empirical P < 0.002) on marker D7S3058.