J. Koochmeshgi, S.M. Hosseini-Mazinani, S.M. Seifati, N. Hosein-Pur-Nobari, L. Teimoori-Toolabi

Apolipoprotein E plays an important role in lipid transport and metabolism. E2/E3/E4 polymorphism of apolipoprotein E (APOE) gene has been implicated in a number of age-associated diseases and conditions- e.g.: Alzheimers, coronary heart disease, and osteoporotic fractures- with APOE 4 allele being associated with these conditions. In an interesting parallel, the age at menopause in women shows a connection with the same age-associated diseases and conditions, an early age at menopause being a risk factor. Also, several recent studies have connected APOE genotype and lifespan, with APOE 4 allele being associated with a shorter lifespan. Taking into consideration that life history studies have linked lifespan with reproductive parameters, we tested the hypothesis that there is a relation between APOE genotype and the age at menopause. We studied a sample of retired female teachers aged between 50 and 60 years who had reached natural menopause. The age at menopause was meticulously determined through clinical history taking and APOE genotype was established by PCR-RFLP method. Survival analysis of data showed a significant relation between APOE genotype and the age at menopause, carriers of APOE 4 allele reaching menopause at a significantly earlier age in comparison to carriers of APOE 3 and APOE 2 alleles. This statistical significance holds after taking into account factors known to influence the age at menopause, such as smoking. Phylogenetic studies have suggested APOE 4 as the ancestral human APOE allele, from which E3 and E2 alleles have been driven. Our findings can have bearing on the question of the evolution of this major human polymorphism and human life history. These findings are also relevant to the question of the connection between age-associated diseases and reproductive parameters.

Keywords (Optional): 
Apolipoprotein E
Life History