Common Genetic Variation in the Sex Steroid Hormone-Binding Globulin (SHBG) Gene and Circulating SHBG Levels among Postmenopausal Women: The Multiethnic Cohort

Publisher Website
Google Scholar
Abstract
SHBGtransportssexsteroidhormonesintheblood,andlevels in humans are thought to partially be genetically determined. Recently, studies have found a pentanucleotide (TAAAA)n re- peat polymorphism in the promoter of the SHBG gene and a missense polymorphism in exon 6 (Asp327Asn) to predict cir- culating SHBG levels. Based on the potential role of common genetic variation in SHBG to serve as a marker of SHBG levels in the general population, we evaluated the association be- tween the (TAAAA)n repeat polymorphism, Asp 327 Asn poly- morphism, and SHBG levels in a population of African- American, Native Hawaiian, Japanese, Latina, and white healthy postmenopausal women from the Multiethnic Cohort Study (n 372). Mean SHBG levels were not significantly different between carriers and noncarriers of the Asn327allele (minor allele frequency range across ethnic groups, 0.02-0.14; Asp/AsnandAsn/Asngenotypes,33.6mol/liter;95%confidence interval(CI),28.2-40.0;n49;Asp/Aspgenotype,30.8mol/liter (95% CI, 28.7-33.1; n 296); P 0.37). For the repeat polymor- phism, we observed six different SHBG repeat alleles segre- gating in the population (TAAAA6-11), and the distribution of these alleles varied widely across populations. We found sug- gestive evidence of linkage disequilibrium between the Asn327 allele and the eight-repeat allele in all populations except African-Americans (P > 0.08). In analysis of the repeat poly- morphism, SHBG levels among carriers of two short alleles (seven or fewer repeats; 31.2 nmol/liter; 95% CI, 27.3-35.6; n 82) were not statistically different from those of carriers of two long alleles (more than seven repeats; 32.7 nmol/liter; 95% CI, 29.4-36.3; n 124; P 0.59). We did, however, observe individualgenotypicclasses(n16)tocontributemodestlyto the overall prediction of SHBG levels (by analysis of covari- ance,P0.03).Carriersofthesix-repeatallele(27.9nmol/liter; 95% CI, 25.2-30.8; n 147) were found to have nominally sig- nificantly lower SHBG levels than noncarriers (32.4 nmol/ liter; 95% CI, 29.7-35.2; n 202; P 0.03). This effect was stronger among the subset of women who also carried the Asn327allele(interaction,P0.006).Insummary,theseresults suggest that genetic variation at the SHBG locus may con- tribute to modest differences in SHBG levels among healthy postmenopausal women, and that much larger studies will be needed to better comprehend the effects of common varia- tions at this locus in predicting circulating SHBG levels. (J Clin Endocrinol Metab 90: 2198-2204, 2005)

This publication has 0 references indexed in Scilit: