Quantitative genetics of serum sex hormone-binding globulin levels in participants in the San Antonio Family Heart Study

Sex hormone-binding globulin (SHBG) is a steroid-binding plasma protein with a high affinity for testosterone that has been inversely associated with cardiovascular disease risk in many populations. SHBG may also act as a receptor in some tissues. Although the function of SHBG is relatively well understood, comparatively little is known about genetic factors contributing to the normal variation of serum SHBG levels. We estimated the heritability (h2) of serum SHBG levels in 717 related Mexican-Americans participating in the San Antonio Family Heart Study (SAFHS). We found a significant heritability (h2 = 0.31, P < .0001) for serum SHBG levels; age, exogenous hormones, smoking status, diabetic status, and adiposity showed significant associations (P < .05) with mean levels of SHBG. Sex was associated with mean SHBG levels but not with genetic or environmental variance in SHBG levels; heritability estimates were the same for males and females. These results indicate a significant genetic influence on SHBG in Mexican-Americans. Thus, SHBG may prove to be an important indicator of genetic risk for cardiovascular disease in this population, as well as others.