The Association of the K121Q Polymorphism of the Plasma Cell Glycoprotein-1 Gene with Type 2 Diabetes and Hypertension Depends on Size at Birth
Agata Kubaszek,
Anu Markkanen,
Johan G. Eriksson,
Tom Forsen,
Clive Osmond,
David J. P. Barker and
Markku Laakso
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 intrauterineenvironment, and a small body size at birth is a predictor oftype 2 diabetes and hypertension. Insulin is one of the growthfactors regulating fetal growth. The plasma cell glycoprotein1 (PC-1) gene impairs insulin signaling at the insulin receptorlevel. Therefore, we investigated whether the K121Q polymorphismof the PC-1 gene association with insulin sensitivity, insulinlevels, and the prevalence of diabetes and hypertension in adultlife depends on size at birth in 489 subjects born in Helsinkiduring 1924–1933. We found that the effect of the PC-1gene polymorphism on insulin levels and insulin sensitivity,measured as the homeostasis model assessment for insulin resistance,depended on birth length because fasting insulin levels andinsulin resistance were highest in subjects carrying the 121Qallele who were small at birth (P for interaction = 0.04 and0.05). Additionally, in those whose birth length was up to 49cm, the K121Q polymorphism of the PC-1 gene was associated witha 2-fold higher incidence of type 2 diabetes. Moreover, subjectswho were short at birth and who had the 121Q allele had thehighest incidence (31.6%) of type 2 diabetes together with hypertension.We conclude that the interaction between the K121Q polymorphismof the PC-1 gene and birth length affects insulin sensitivityand increases susceptibility to type 2 diabetes and hypertensionin adulthood.
This work was supported by the British Heart Foundation, FinskaLakaresallskapet, the Academy of Finland, and the European Union(QLG1-CT-1999).
Abbreviations: BMI, Body mass index; HOMA-IR, homeostasis modelassessment for insulin resistance; IR, insulin receptor; PC-1,plasma cell glycoprotein 1.
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