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American Journal of Epidemiology Advance Access published online on December 4, 2007
American Journal of Epidemiology, doi:10.1093/aje/kwm332
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American Journal of Epidemiology © The Author 2007. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

Original Contribution

Associations of Serum Sex Hormone Binding Globulin (SHBG) Levels with SHBG Gene Polymorphisms in the CARDIA Male Hormone Study

Andrew Turk1, Peter Kopp2,3, Laura A. Colangelo4, Margrit Urbanek2,3, Kent Wood5, Kiang Liu4, Halcyon G. Skinner6 and Susan M. Gapstur3,4

1 Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY
2 Department of Medicine, Center for Endocrinology, Metabolism and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL
3 Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL
4 Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL
5 Department of Pharmacology and Cancer Biology, Duke University Graduate School, Durham, NC
6 Department of Population Health Sciences and the Paul C. Carbone Comprehensive Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, WI

Correspondence to Dr. Susan M. Gapstur, Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, 680 N. Lake Shore Dr., Suite 1102, Chicago, IL 60611 (e-mail: sgapstur{at}northwestern.edu).

Received for publication August 9, 2007. Accepted for publication October 17, 2007.

In the sex hormone binding globulin (SHBG) gene, a pentanucleotide-repeat polymorphism [(TAAAA)n] and a single nucleotide polymorphism (D327N) have been associated with circulating SHBG concentrations in women. Only one study, limited to Scandinavians, has examined these associations in men. Using data from the Coronary Artery Risk Development in Young Adults (CARDIA) Male Hormone Study, the authors assessed associations of SHBG polymorphisms with serum SHBG levels in 511 Black men and 698 White men who had SHBG measured in multiple serum samples collected over an 8-year period from 1987 to 1996 and were aged 20–34 years at the time of the first SHBG measurement. Multivariable repeated-measures analyses were used to assess associations of (TAAAA)n and D327N polymorphisms with SHBG concentrations. Results showed statistically significant differences in mean SHBG concentrations for White men with genotypes of (TAAAA) 6/6 (35.1 nmol/liter), 6/x (30.8 nmol/liter), and x/x (29.6 nmol/liter), where x represents a repeat length greater than 6 (p = 0.001). For Black men, the pattern of association was similar, albeit not statistically significant (p = 0.35). There was no relation between D327N genotype and SHBG levels. These results suggest that the (TAAAA)n repeat length in the SHBG gene, but not the D327N variant, might contribute to the interindividual variability in serum SHBG levels.

men; polymorphism, genetic; sex hormone-binding globulin

Abbreviations: CARDIA, Coronary Artery Risk Development in Young Adults; PCR, polymerase chain reaction; SHBG, sex hormone binding globulin


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