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The Association of the K121Q Polymorphism of the Plasma Cell Glycoprotein-1 Gene with Type 2 Diabetes and Hypertension Depends on Size at Birth

Department of Medicine (A.K., A.M., M.L.), University of Kuopio, 70210 Kuopio, Finland; National Public Health Institute (J.G.E.), Department of Epidemiology and Health Promotion, 00300 Helsinki, Finland; Department of Public Health (T.F.), University of Helsinki, 00300 Helsinki, Finland; and MRC Environmental Epidemiology Unit (C.O., D.J.P.B.), University of Southampton, Southampton General Hospital, 5016 6YD Southampton, United Kingdom

Address all correspondence and requests for reprints to: Markku Laakso, Professor and Chair, Department of Medicine, University of Kuopio, 70210 Kuopio, Finland. E-mail: markku.laakso{at}kuh.fi.

Birth weight and length serve as indicators of the intrauterine environment, and a small body size at birth is a predictor of type 2 diabetes and hypertension. Insulin is one of the growth factors regulating fetal growth. The plasma cell glycoprotein 1 (PC-1) gene impairs insulin signaling at the insulin receptor level. Therefore, we investigated whether the K121Q polymorphism of the PC-1 gene association with insulin sensitivity, insulin levels, and the prevalence of diabetes and hypertension in adult life depends on size at birth in 489 subjects born in Helsinki during 1924–1933. We found that the effect of the PC-1 gene polymorphism on insulin levels and insulin sensitivity, measured as the homeostasis model assessment for insulin resistance, depended on birth length because fasting insulin levels and insulin resistance were highest in subjects carrying the 121Q allele who were small at birth (P for interaction = 0.04 and 0.05). Additionally, in those whose birth length was up to 49 cm, the K121Q polymorphism of the PC-1 gene was associated with a 2-fold higher incidence of type 2 diabetes. Moreover, subjects who were short at birth and who had the 121Q allele had the highest incidence (31.6%) of type 2 diabetes together with hypertension. We conclude that the interaction between the K121Q polymorphism of the PC-1 gene and birth length affects insulin sensitivity and increases susceptibility to type 2 diabetes and hypertension in adulthood.

This work was supported by the British Heart Foundation, Finska Lakaresallskapet, the Academy of Finland, and the European Union (QLG1-CT-1999).

Abbreviations: BMI, Body mass index; HOMA-IR, homeostasis model assessment for insulin resistance; IR, insulin receptor; PC-1, plasma cell glycoprotein 1.

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