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AAPS PharmSci. Dec 2003; 5(4): 49–61.
Published online Nov 5, 2003. doi:  10.1208/ps050429
PMCID: PMC2750991
Pharmacogenomics of multigenic diseases: Sex-specific differences in disease and treatment outcome
Julia Pinsonneaultcorresponding author and Wolfgang Sadéecorresponding author
Department of Pharmacology, Ohio State University, 333 W. 10th Avenue, 43210 Columbus, OH
Wolfgang Sadée, Phone: (614) 292-1597, Fax: (614) 292-7232, sadee-1/at/medctr.osu.edu.
corresponding authorCorresponding author.
Received August 5, 2003; Accepted September 15, 2003.
Numerous genetic variations have been shown to affect disease susceptibility and drug response. Pharmacogenomics aims at improving therapy on the basis of genetic information for each individual patient. Furthermore, sex chromosomes broadly determine biological differences between males and females. Consequently, substantial sex differences exist in phenotypic manifestation of disease and treatment response. This review discusses the role of sex in coronary artery disease, schizophrenia, and depression—complex multigenic disorders with considerable sex differences in frequency and presentation. Moreover, genetic factors underlying disease and drug response appear to differ between male and female patients. This appears to result at least in part from different physiological effects exerted by sex hormones such that polymorphisms in susceptibility genes may have physiological relevance only in males or females. However, few examples have been discovered to play a role in complex multigenic diseases, and the mechanistic basis of genetic variants as sex-dependent susceptibility factors has yet to be explored. Therefore, pharmacogenomic studies must consider sex differences in an effort to optimize individual drug therapy.
Keywords: pharmacogenomics, sex differences, multigenic disease, candidate genes, coronary artery disease, depression, schizophrenia
Footnotes
An abbreviated version of this article, entitled “Pharmacogenomics: Sex Matters”, has been published in AAPS Newsmagazine, July 2003;6(7): 18–21, 44.
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