Jeanette McCarthy, PhD
Associate Professor, Track V, Department of Community and Family Medicine
Many human traits exhibit sexual dimorphism, where the prevalence and perhaps etiology differs between men and women. When the effect of a genetic risk factor on a trait or disease is significantly different in men and women, gene by sex interaction exists. The McCarthy lab is involved in characterizing gene by sex interaction in the etiology of lipid disturbances and metabolic syndrome. Using a combination of epidemiological and genomic approaches applied to human populations, we are studying the genome-wide occurrence of gene by sex interaction for dyslipidemias, and the mediating effects of sex hormones on these interactions. Through our work, we have identified genetic variants in the scavenger receptor, SCARB1, that exhibit gene by sex interaction for lipid traits and have shown that estrogens (either endogenous or exogenous) mediate this effect. These findings have implications for women taking post-menopausal estrogen therapy and may provide the basis for future pharmacogenomic tests used to reduce cardiovascular side effects of estrogen therapy.
A major focus of our work is the dyslipidemia associated with chronic hepatitis C virus (HCV) infection, where infected individuals experience a decline in all lipids, especially apolipoprotein B. Working closely with Duke GI/Hepatologist John McHutchison, we are exploring the link between HCV dyslipidemia and outcomes of HCV infection including development of liver fibrosis and response to therapy and the genetic basis of HCV associated dyslipidemia. Of particular interest is the observed sexual dimorphism in outcomes of HCV infection: women, especially premenopausal women, have slower rates of disease progression and are more likely to respond to therapy. We are currently investigating whether sexual dimorphism extends to HCV dyslipidemia and the implications for management of HCV infection.