Genetics of menopause-associated diseases

Menopause is the permanent cessation of menstruation resulting from the los s of ovarian follicular activity. It is estimated that perhaps 50 million w omen worldwide will go into menopause annually. Atherosclerotic cardiovascu lar disease, osteoporotic fractures and Alzheimer's dementia are common chr onic disorders after menopause, representing major health problems in most developed countries. Apart From being influenced by environmental factors, these chronic disorders recognize a strong genetic component. and there are now considerable clinic evidences that these disorders are related to low hormonal milieu of postmenopausal women. Here. we review up-to-date availab le data suggesting that genetic variation may contribute to higher suscepti bility to four sporadic chronic syndromes such as osteoporosis (OP), osteoa rthritis (OA). Alzheimer's disease (AD) and coronary artery disease (CAD). For these four syndromes candidate genes that today appear as major loci in genetic susceptibility encode for proteins specific of a given system, as the vitamin D receptor (VDR) gene for the skeleton and, therefore, OP or an giotensin converting enzyme (ACE) for the cardiovascular system and, theref ore, CAD. The investigation of gene polymorphisms in various pathological c onditions typical of postmenopause offer an explanation not only of their g enetic inheritance but also of their co-segregation in given individuals. I n this view, it may be possible to identify a common set of genes whose var iants contribute to a common genetic background for these different disorde rs. Ideal candidates appear genes of the estrogen response cascade [i.e. es trogen receptor (ERs), enzymes involved in estrogen metabolism or co-activa tors and co-inhibitors]. All together this information may represent the ba sis both for future recognition of individuals at risk and for the pharmaco genetic driving of drug responsiveness. (C) 2001 Elsevier Science Ireland L td. All rights reserved.