The K121Q variant of the human PC-1 gene is not associated with insulin resistance or type 2 diabetes among Danish Caucasians

The human plasma-cell membrane differentiation antigen-1 (PC-1) has been sh own to inhibit insulin receptor tyrosine kinase activity. Recently, a K121Q polymorphism in the human PC-1 gene was found in a Sicilian population and was shown to be strongly associated with insulin resistance. The objective s of the present investigation were to examine in the Danish Caucasian popu lation whether the K121Q variant was associated with type 2 diabetes or, in glucose-tolerant subjects, with impaired whole-body insulin sensitivity. W e genotyped 404 Danish type 2 diabetic patients and found that the allele f requency of the variant was 0.14 (95% CI 0.12-0.16), whereas the allele fre quency was 0.16 (95% CI. 0.13-0.19) among 237 matched glucose-tolerant cont rol subjects (P = 0.6), In the control subjects, there were no significant differences among wild-type, heterozygous, or homozygous subjects in regard to 1) serum insulin and plasma glucose levels at fasting, 60 min, or 120 m in during an oral glucose tolerance test (OGTT) or 2) the estimates of insu lin resistance obtained from the homeostasis model assessment (HOMA), Furth ermore, we investigated the impact of the variant in 2 other Danish populat ion samples that comprised 356 young healthy subjects and 226 glucose-toler ant offspring of type 2 diabetic probands, respectively. In all of the stud y populations, the polymorphism was not associated with an altered insulin sensitivity index as estimated from an intravenous glucose tolerance test i n combination with an intravenous injection of tolbutamide, In addition, am ong the 226 offspring,, the variations in serum insulin and serum C-peptide responses measured during an OGTT were not related to the PC-1 genotype. I n conclusion, the K121Q polymorphism of the human PC-1 gene is not associat ed with type 2 diabetes or insulin resistance among Danish Caucasians.