Gender Specificity, Genetic Variation of Single Nucleotide Polymorphisms, and Blood Lipid Parameters

Gender specificity of the clinical presentation and the course of diseases may - at least in part - be mediated by polymorphic genetic variation. In addition, different pharmacogenetic effects in men and women may be accounted for by the carriage of polymorphisms. A variety of studies have investigated these issues with respect to blood lipids and found clear indications for gender-specific effects depending on the carriage of particular alleles. For example, apolipoprotein E (APOE) 2 gene-treatment interactions for statin therapy with atorvastatin were observed in men, but not in women. The risk for myocardial infarction while taking simvastatin is modulated by the APOE 4 allele in men, but not in women. Gene-environment interactions between alcohol use and LDL cholesterol levels are dependent on the APOE genotype exclusively in men. In addition, the APOE genotype significantly influences bone mineral density at the hip and lumbar spine dependent on hormone replacement status. Variance in the apolipoprotein A (APOA) 5 gene influences triglyceride levels in both men and women, but in different ways. Besides the activities and effects of apolipoproteins, research has demonstrated that hormone sensitive lipase is also genetically controlled with pronounced gender-specific variations. While it seems clear that gender specificity and genetic variation due to polymorphisms are interrelated phenomena, the functional reason for these gender-specific effects is unknown. Data in the literature show that the distribution of specific alleles and genotypes is not different between men and women. Thus, other factors have been advocated, namely the influence of sex steroids on expression patterns and effects of genes and gene products, respectively.