Association of CYP19 and ESR1 pleiotropic genes with human longevity.

Aromatase (CYP19) and estrogen receptor-alpha (ESR1) are involved in the metabolism of estrogens, which have a relevant role in female and male aging. Moreover, due to their influence on fertility, both genes may be part of the longevity-fertility trade-off mechanism. This investigation examines the association of ESR1 (PvuII and XbaI) and CYP19 (rs4646) polymorphisms with longevity.

Association of ACE I/D polymorphism and recurrent miscarriages in an Italian population with a pre-modern reproductive pattern.

Angiotensin I-converting enzyme (ACE), in addition to its role in the renin angiotensin system, has a physiological function in the fibrinolysis pathway, the accurate control of which is critical for the normal development of pregnancy. Recently, the ACE I/D polymorphism was found to be associated with recurrent spontaneous miscarriages (RM). The present study analysed the relationship between ACE I/D polymorphism and the number of spontaneous miscarriages, the number of pregnancies and the number of children in a sample of 88 Italian women born before 1930, with a pre-modern reproductive behaviour.

Genetic variation of CYP19 (aromatase) gene influences age at onset of Alzheimer's disease in women.

Background/aims: There is evidence for a higher prevalence of Alzheimer's disease (AD) in women, but whether this is due to their longer life expectancy or to biological gender-specific risk factors is unclear. One likely contributing factor is the reduced estrogen neuroprotective action following menopause. In this context, an AD risk gene could be CYP19, encoding aromatase, an enzyme involved in estrogen biosynthesis.

Study on a possible effect of four longevity candidate genes (ACE, PON1, PPAR-gamma, and APOE) on human fertility.

The present study investigated for a possible effect on fertility of four longevity candidate genes (ACE, PON1, PPAR-gamma, APOE) in order to determine whether they have a pleiotropic action at different life ages. The study population was 151 healthy unrelated subjects. Only PPAR-gamma and APOE showed an effect on fertility.

Combined effect of apolipoprotein e genotype and past fertility on age at onset of Alzheimer's disease in women.

Background: Various risk factors influence the development of Alzheimer's disease (AD). Apolipoprotein E (APOE) e*4 allele has a major role in AD susceptibility and its presence reduces age at AD onset. APOE is also thought to influence human reproduction, and common APOE genotypes seem to be associated with differential fertility.

Estrogen receptor alpha polymorphisms and fertility in populations with different reproductive patterns.

The estrogen receptor (ER) plays an important role in mediating estrogen action on target tissues. ER-alpha, the most abundant, is found in all human reproductive tissues and studies on alpha-ER knockout mice have highlighted its role in reproduction. ER-alpha gene (ESR1) polymorphisms have been associated with a variety of disorders including human infertility.

Apolipoprotein E polymorphism and fertility: a study in pre-industrial populations.

Human apolipoprotein E is the most important supplier of the cholesterol precursor for steroid hormone production in steroidogenic tissues and therefore could play a role in the regulation of steroid hormone function and influence human reproduction. This hypothesis has been confirmed by studies describing a differential fertility associated with common apolipoprotein (APOE) genotypes in two European populations. In the present investigation the impact of APOE genetic variation on fertility was studied in two Ecuadorian populations, African-Ecuadorians (57 women) and Cayapa Indians (27 women).

Environmental factors and the proportion of males at birth in Italy.

A significant decline in the proportion of male births has been observed in recent decades in several western countries, and several researchers have raised the question of the possible role of environmental pollution in this trend. In the present analysis, the authors examined the effect of environmental factors (pollution from pesticides, urban pollution, and industrial pollution) on the sex ratio (proportion of males) of Italian singleton 1st births for the years 1989-1993, controlling for the age of the mother. The data show a slight increase in the sex ratio from north to south; however, no reduction in the proportion of males was seen in areas with higher pesticide consumption or intense industrial pollution.

Sex differential patterns in perinatal deaths in Italy.

In industrialized countries, male excess is generally found in early deaths, despite the overall decrease in mortality. We studied the association between sex and some factors generally considered crucial for babies' survival, such as mother's age and education, birth order, and gestational age, in order to gain insight into the causes underlying the persisting higher vulnerability of male sex in early life. The analysis was performed on babies dying during the perinatal period.

Changes in twinning rate: Italy 1950-1996.

Background: In the wide-ranging debate about the potential monitors of population fertility, twinning rate has been considered a candidate. In the developed countries, a decline in spontaneous twinning rate began around 1950 and continued until the late 1970s. The decrease in mean maternal age at delivery and the number of children per family have been considered as possible reasons for the decrease.

Absence of selection on birth weight in modern Italy.

The effect of stabilizing and directional selection on birth weight has been analyzed for Italian births from 1954 to 1994, a period of rapid improvement in environmental conditions. The population of newborns was subdivided according to gestational age, one of the main covariates of birth weight. In the last cohort of births, no selection at all (neither stabilizing nor directional) was found in full-term babies, which represent more than 95% of total deliveries.

Trends in childbearing and stillbirth risk: heterogeneity among Italian regions.

In Italy, as in all Western countries, the almost monotonic decline in fertility observed since the 1960s has been paralleled until the beginning of the 1980s by a decrease in maternal age at delivery. Since then, age at marriage and at childbearing has been increasing and marital fertility has continued to decrease. By 1994 Italy showed extreme values of low total fertility rate (1.

Sex ratio at reproductive age: changes over the last century in the Italian population.

The radical improvement in living conditions experienced in Italy during the last century caused a reduction in male extra-mortality during the prereproductive years. As a consequence, a progressive increase in the sex ratio at the beginning of the reproductive age (15-19 years) occurred, so that in recent times the sex ratio in the young adult population has approached the almost constant value of 1.06 observed at birth.

Natural selection and reproductive behavior in Italy, 1930-1993.

We studied the relaxation of natural selection affecting the newborn population in Italy between 1930 and 1993 due to the decrease in the stillbirth (mortality) rate and the simultaneous changes in women's reproductive behavior (strategies). Results show that, apart from a drastic overall reduction, the stillbirth rate has varied among different groups of neonates. The present stillbirth rate of less than 5 per thousand, observed in 8 of the 20 phenotypic classes defined on the basis of maternal age at delivery and neonate birth order, most likely represents an unavoidable biological or genetic cost.

Natural selection in industrialized countries: a study of three generations of Italian newborns.

We have studied the impact of natural selection on the Italian population, analysing the relationship between stillbirth and three related variables: birth weight, birth order and maternal age. A progressive relaxation of selection with time has been demonstrated by the reduction of the Haldane index calculated with respect to the three variables.

Heterogeneous effects of natural selection on the Italian newborns.

We have studied the impact of natural selection through stillbirth on the Italian population, taking into account the socio-economic heterogeneity of the country. The results suggest that older age at delivery and lower cultural level of the mothers, indicators of critical biological and socio-economic conditions, even at present increase stillbirth risk. Moreover, in the less favourable environment of the southern regions, selection is still sex-specific.

Genetic fitness in Huntington's Disease and Spinocerebellar Ataxia 1: a population genetics model for CAG repeat expansions.

An analysis of genetic fitness was performed in Huntington's Disease (HD) and Spinocerebellar Ataxia 1 (SCA1) families. Two partially overlapping samples were used: clinically defined HD and SCA1 patients from families ascertained in definite geographical areas, and molecularly typed carriers of HD and SCA1 mutations (CAG trinucleotide expansions). In both cases, a control group of normal relatives was used.

Early selection and sex composition in Italy: a study at the regional level.

We have chosen four Italian regions with different degrees of industrialization and socioeconomic levels to study environmental differences in the sex ratio. The improvement in living and sanitary conditions during the last century has led to a progressive reduction in early male extramortality, and the sex ratio at birth has been almost unchanged at least to the first year of life and probably up to reproductive age. To investigate whether socioeconomic, cultural, or biological factors still influence the sex ratio at birth, we studied the stillbirth rate and the relations between newborn viability and sex composition as a function of maternal age and educational level.

Factors affecting the sex ratio in humans: multivariate analysis of the Italian population.

Several studies have shown that the human secondary sex ratio is affected by a wide range of biological and environmental factors. Here, we describe a partitioning of the sex ratio variability as observed in the Italian population over the last two generations. This period has seen drastic changes in the environmental conditions of Italy.

Sex ratio and selection by early mortality in humans: fifty-year analysis in different ethnic groups.

We studied the sex ratio (M/F) in representative populations of the main human ethnic groups, namely, US whites, US blacks, and Japanese. The data cover a period of over 50 years. For intra-ethnic comparison, we included analogous data on Italians.

Sex ratio and natural selection in humans: a comparative analysis of two Caucasian populations.

In the course of the last century industrialized countries have experienced significant changes in mortality rates. Since the sex ratio of a population may be considered a function of, among other factors, differential mortality in the two sexes, it is expected to correlate with changes in sex-specific mortality rates. In this paper secular changes in the sex ratio at birth and after the action of relevant components of early selection (stillbirth, mortality within the first month and within the first year of life) have been studied in the Italian and in the USA White populations.

Effects of environmental changes on natural selection active on human polygenic traits.

During the last century, industrialized countries experienced such an improvement in socioeconomic conditions and in sanitation that it is likely that the selective forces active on human metric traits have been modified. Perinatal mortality as a function of birth weight is one of the clearest examples of natural selection in humans. Here, trends over time of stabilizing and directional selection associated with birth weight have been analyzed in Japan from 1969 to 1989.

Natural selection associated with birth weight. VI. Towards the end of the stabilizing component.

The secular trend for stabilizing selection on birth weight has been analysed in Italy from 1954 to 1985 in order to study changes in the forces of natural selection which have occurred as a consequence of progress in health care. In previous papers we demonstrated a very rapid relaxation of stabilizing selection on birth weight. In this paper we show that in the last few years this kind of selection has been coming to an end for the vast majority of Italian newborns.

Effects of environmental changes on the phenotypic expression of human polygenic traits.

The very large increase in adult stature during the last century is well documented for many countries and this phenomenon has been associated with the rapid improvement of environmental conditions. In the case of Italy, data relative to its regions and drawn from the military records of the last century showed a rapid normalization (i.e.