Differential reproductive efficiency associated with common apolipoprotein e alleles in postreproductive-aged subjects.

OBJECTIVE: To investigate the possible impact of apolipoprotein E (APOE) polymorphism on reproductive efficiency. DESIGN: Population study. SETTING: University Departments and a Laboratory of National Research Council. PATIENT(S): One hundred sixty healthy unrelated subjects of postreproductive age. INTERVENTION(S): Peripheral blood collection and questionnaire administration. MAIN OUTCOME MEASURE(S): Apolipoprotein E genotypes were detected after PCR amplification and CfoI digestion; plasma total cholesterol was assayed. RESULT(S): The mean number of children of e*2 allele carriers (2.4) was lower than that of e*3/e*3 and e*4/e*3 subjects (3.9). The trend was similar (2.8 vs. 4.8) when the number of pregnancies was considered. Moreover, there was a clear inverse relationship between number of children and e*2-carrying genotype proportions (chi(2) for trend = 6.3). Conversely, the e*3/e*3 genotype was associated with the highest number of children and pregnancies (3.9 and 4.9, respectively), and the e*4/e*3 genotype, with intermediate values (3.7 and 4.4). Carriers of e*2 allele also showed the lowest levels of total cholesterol. CONCLUSION(S): The e*2 allele seems to be associated with the lowest reproductive efficiency and the e*3 allele, with the highest. The different total cholesterol levels associated with APOE genotypes could have an effect on steroidogenesis and determine as a consequence the observed differential fertility.

Alpha2-macroglobulin deletion polymorphism and plasma levels in late onset Alzheimer's disease.

The acute-phase "panproteinase" inhibitor alpha2-macroglobulin (alpha2M), a protein involved in inflammatory reactions, has been identified in amyloid plaques in Alzheimer's disease (AD). In addition, alpha2M is involved in AD susceptibility at the genetic level, and a deletion polymorphism at the a2M gene has been found to be associated with sporadic AD. We analyzed the deletion polymorphism and alpha2M plasma levels in 93 ultraoctuagenarian patients with late-onset sporadic AD and in controls (n=157). alpha2M allele frequencies did not differ between AD patients (alpha2M*2=0.169) and controls (alpha2M*2=0.146). The mean plasma concentrations of alpha2M were similar in patients (271.8+/-79 mg/dl) and controls (269.5+/-81.2 mg/dl). No difference was found in the alpha2M mean plasma levels associated with the three alpha2M genotypes, indicating that the deletion has no effect on alpha2M protein level. However, in AD patients alpha2M mean plasma values differed significantly according to apolipoprotein E genotypes (p=0.03), with E3/E3 homozygotes showing the highest levels. Since in a previous work E3/E3 were found to be associated with the highest plasma levels of alpha1-antichymotrypsin, another acute-phase protein, the present findings seem to support the hypothesis that inflammation may be a relevant factor in AD pathogenesis peculiar to E3/E3 subjects.