The human plasma-cell membrane differentiation antigen-1 (PC-1) has been shown 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 objectives of the present investigation were to examine in the Danish Caucasian population whether the K121Q variant was associated with
type 2 diabetes or, in
glucose-tolerant subjects, with impaired whole-body
insulin sensitivity. We genotyped 404 Danish type 2 diabetic patients and found that the allele frequency of the variant was 0.14 (95% CI 0.12-0.16), whereas the allele frequency was 0.16 (95% CI 0.13-0.19) among 237 matched
glucose-tolerant control 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 min during an oral
glucose tolerance test (OGTT) or 2) the estimates of
insulin resistance obtained from the homeostasis model assessment (HOMA). Furthermore, we investigated the impact of the variant in 2 other Danish population samples that comprised 356 young healthy subjects and 226
glucose-tolerant offspring of type 2 diabetic probands, respectively. In all of the study populations, the polymorphism was not associated with an altered
insulin sensitivity index as estimated from an intravenous
glucose tolerance test in combination with an
intravenous injection of
tolbutamide. In addition, among 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. In conclusion, the K121Q polymorphism of the human PC-1 gene is not associated with
type 2 diabetes or
insulin resistance among Danish Caucasians.