Published Online
on February 20, 2003

A more recent version of this article appeared on March 1, 2003

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Submitted on September 11, 2002
Accepted on October 4, 2002

Associations of a Human G Protein 3 Subunit Dimorphism With Insulin Resistance and Carotid Atherosclerosis

Thomas C. Wascher MD^*; Bernhard Paulweber MD; Liliane Malaimare MD; Andreas Stadlmayr MD; Bernhard Iglseder MD; Isabella Schmoelzer MD; and Wilfried Renner PhD

From the Department of Internal Medicine, Diabetic Angiopathy Research Group, University of Graz, Graz, Austria (T.C.W., I.S., W.R.), and First Department of Internal Medicine (B.P., L.M., A.S.) and Department of Neurology (B.I.), Landeskliniken Salzburg, Salzburg, Austria.

^* To whom correspondence should be addressed. E-mail: thomas.wascher{at}kfunigraz.ac.at.

Background and Purpose--The C825T dimorphism of the gene encoding the human G protein 3 subunit (GNB3) is associated with hypertension and obesity. Although these findings suggest an association with insulin resistance and atherosclerosis, this hypothesis has yet been tested only partially.

Methods--To investigate this hypothesis, the C825T dimorphism was determined in a population of 932 middle-aged white subjects of middle European (Austrian) origin. Insulin sensitivity was measured with the short insulin tolerance test; intima-media thickness of the carotid artery and morphological plaque burden were measured by ultrasound.

Results--Insulin sensitivity was found to be significantly lower in carriers of the T allele (3.55±1.27 versus 3.92±1.30%/min, P=0.012) in the group of male subjects with abdominal body fat distribution (waist-to-hip ratio >0.9). No effect was observed in women or men with a waist-to-hip ratio <0.9. Advanced carotid artery plaques were more frequent (odds ratio, 1.606; 95% confidence interval, 1.002 to 2.575; P=0.04) in carriers of the T allele regardless of sex. No effect was observed with regard to carotid artery intima-media thickness.

Conclusions--In summary, our results demonstrate that the GNB3 825T allele is associated with reduced insulin sensitivity in men with abdominal fat distribution and with more advanced carotid atherosclerosis in middle-aged white men and women.

Key words: atherosclerosis • genetics • insulin • proteins

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