Aging and genetic variation of plasma apolipoproteins. Relative loss of the apolipoprotein E4 phenotype in centenarians.

Abstract

We determined the common polymorphism of apolipoprotein E (E2, E3, and E4), apolipoprotein B Xba I polymorphism, and apolipoprotein C-III Sst I polymorphism in almost all Finnish centenarians alive in 1991 (n=179/185). Plasma lipid and lipoprotein levels in different apolipoprotein genotypes were also measured. In comparison with younger Finnish populations studied previously, the frequency of the apolipoprotein E e2 allele was almost twice as high (7.0% versus 4.1%; P<.05) and that of the e4 allele only approximately one third as high (8.4% versus 22.7%; P<.001) in the centenarians. Plasma cholesterol and high-density lipoprotein cholesterol levels tended to be lowest in the group with the e2 allele (4.33 mmol/L and 1.41 mmol/L, respectively), intermediate in those with the e3 allele (4.57 mmol/L and 1.48 mmol/L, respectively), and highest in those with the E4 allele (4.82 mmol/L and 1.60 mmol/L, respectively). The frequencies of the apolipoprotein B XI and X2 alleles (Xba I restriction A polipoproteins occupy a central position in lipo-/ \ protein metabolism. Apolipoprotein E (apoE) A. \ _ is present in chylomicrons and very-low-density lipoprotein and their lipolytic degradation products, ie, chylomicron remnants and intermediate-density lipoproteins. -2 It also plays a role in cholesterol absorption and in the receptor-mediated uptake of lipoprotein particles by the liver. Apolipoprotein B (apoB) is essential for the synthesis and secretion of chylomicrons in the intestine and of VLDL in the liver and serves as the ligand allowing the low-density lipoprotein (LDL) receptor to recognize LDL.1 ' 2 Apolipoprotein C-III (ApoC-III) is a major protein constituent of triglyceride-rich lipoproteins and may also affect the activities of lipoprotein and hepatic Upases. Common genetic polymorphisms of apoE, apoB, and apoC-III have been found to influence serum lipid levels in several populations (for reviews, see References 2 through 6). Three major apoE isoforms (E2, E3, and E4), encoded by three separate alleles (E2, E3, and e4), in different combinations determine six different phenotypes. 57 Several studies have indicated that the e4

Association of apolipoprotein E polymorphism with plasma lipids and Alzheimer's disease in a Southern Brazilian population

“…The relative frequency of APOE*4 was decreased and that of APOE*2 was higher in the oldest subjects (octogenarians, nonagenarians and centenarians) compared to normal subjects of a younger age group (28)(29)(30).…”

Apolipoprotein E and mortality in African-Americans and Yoruba

“…Schacter et al and Louhija et al have found smaller frequencies of the ApoE ε4 allele in French and Finnish centenarians compared to younger cohorts, suggesting an increased mortality with ApoE ε4 [11,16]. Corder et al found in subjects 75-85 years old with and without cognitive impairment and cognitively impaired subjects 85 years or older that ApoE did not significantly predict survival, while among 85 year or older subjects with good cognition, mortality increased with a ε3/ε4 genotype and decreased with an ε2/ε3 genotype relative to the ε3/ε3 genotype [1].…”

ApoE gene and exceptional longevity: Insights from three independent cohorts

“…However, others found no association of this variant with EL in Japanese (Asada et al, 1996), Finnish (Louhija et al, 2001) or Southern-Italian centenarians (Capurso et al, 2004). Concurrently, the ApoE ε2-allele has been reported to be more frequent in centenarians (Blanche et al, 2001;Louhija et al, 1994;Schachter et al, 1994;Seripa et al, 2006) than in younger people, but others found no differences (Asada et al, 1996;Feng et al, 2011;Louhija et al, 2001;Panza et al, 1999). A meta-analysis reported a point estimate of 1.50 [95% confidence intervals (CI): 1.27, 1.78] and 0.49 (95%CI: 0.41, 0.58) for the frequency of ε2 and ε4-alleles, respectively, in centenarians vs. younger controls, but only studies published before 2004 were included in the review (Lewis and Brunner, 2004).…”

“…The majority of reports indicate a lower frequency of the ApoE ε4-allele in centenarians compared with younger controls, i.e., in French (Blanche et al, 2001;Schachter et al, 1994), Finnish (Louhija et al, 1994), Southern Italian (Panza et al, 1999), or Chinese cohorts (Feng et al, 2011). However, others found no association of this variant with EL in Japanese (Asada et al, 1996), Finnish (Louhija et al, 2001) or Southern-Italian centenarians (Capurso et al, 2004).…”