Polymorphisms at the Werner locus: I. Newly identified polymorphisms, ethnic variability of 1367Cy/Arg, and its stability in a population of Finnish centenarians

Castro, Elena; Ogburn, Charles E.; Hunt, Kristin E.; Tilvis, Reijo S.; Louhija, Jukka; Penttinen, Risto; Erkkola, Risto; Panduro, Arturo; Riestra, Roberto; Piussan, C; Deeb, Samir S.; Wang, Lan; Edland, Steven D.; Martin, George M.; Oshima, Junko

doi:10.1002/(sici)1096-8628(19990219)82:5<399::aid-ajmg8>3.0.co;2-r

Cited by 67 publications

(46 citation statements)

References 16 publications

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“…A total of 2075 blood and buccal cell samples were collected to assess the effects of selected genetic markers on human longevity and physical function. The APOE ε2, ε3 and ε4 alleles were determined by the presence or absence of certain restriction sites [23]. Assays were done for 1805 individuals.…”

Section: The 1999 Nltcs Sample With Apoe Informationsupporting

confidence: 72%

Health‐Protective and Adverse Effects of the Apolipoprotein E ɛ2 Allele in Older Men

Kulminski

Ukraintseva

Arbeev

et al. 2008

J American Geriatrics Society

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OBJECTIVES: To reexamine a health‐protective role of the common apolipoprotein E (APOE) polymorphism focusing on connections between the APOEɛ2—containing genotypes and impairments in instrumental activities of daily living (IADLs) in older (≥65) men and women and to examine how diagnosed coronary heart disease (CHD), Alzheimer's disease, colorectal cancer, macular degeneration, and atherosclerosis may mediate these connections. DESIGN: Retrospective cross‐sectional study. SETTING: The unique disability‐focused data from a genetic subsample of the 1999 National Long Term Care Survey linked with Medicare service use files. PARTICIPANTS: One thousand seven hundred thirty‐three genotyped individuals interviewed regarding IADL disabilities. MEASUREMENTS: Indicators of IADL impairments, five geriatric disorders, and ɛ2‐containing genotypes. RESULTS: The ɛ2/3 genotype is a major contributor to adverse associations between the ɛ2 allele and IADL disability in men (odds ratio (OR)=3.09, 95% confidence interval (CI)=1.53–6.26), although it provides significant protective effects for CHD (OR=0.55, 95% CI=0.33–0.92), whereas CHD is adversely associated with IADL disability (OR=2.18, 95% CI=1.28–3.72). Adjustment for five diseases does not significantly alter the adverse association between ɛ2‐containing genotypes and disability. Protective effects of the ɛ2/3 genotype for CHD (OR=0.52, 95% CI=0.27–0.99) and deleterious effects for IADLs (OR=3.50, 95% CI=1.71–7.14) for men hold in multivariate models with both these factors included. No significant associations between the ɛ2‐containing genotypes and IADL are found in women. CONCLUSION: The ɛ2 allele can play a dual role in men, protecting them against some health disorders, while promoting others. Strong adverse relationships with disability suggest that ɛ2‐containing genotypes can be unfavorable factors for the health and well‐being of aging men.

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Section: The 1999 Nltcs Sample With Apoe Informationsupporting

confidence: 72%

Health‐Protective and Adverse Effects of the Apolipoprotein E ɛ2 Allele in Older Men

Kulminski

Ukraintseva

Arbeev

et al. 2008

J American Geriatrics Society

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“…The ε4-allele frequency in our Spanish (10%) and Italian (8%) young controls was relatively higher than that previously reported by Lewis and Brunner (2004) in Southern Europe. Whereas, the ApoE ε4-allele frequency in Spanish and Italian centenarians was 4.9 and 3.2% respectively, which is within the range of previously published frequencies (1-10%) for European centenarians (Blanche et al, 2001;Capurso et al, 2004;Castro et al, 1999;Gerdes et al, 2000;Louhija et al, 1994;Maruszak et al, 2012;Panza et al, 1999;Panza et al, 2003;Schachter et al, 1994;Seripa et al, 2006). On the other hand, allele frequencies in the Japanese centenarians studied here (ε2 = 7.3%; ε3 = 88.1%; ε4 = 4.6%) are comparable to those previously reported in centenarians of the same country, e.g., ε2 = 4.5%; ε3 = 90.9%; ε4 = 4.5% (Asada et al 1996).…”

Section: Discussionmentioning

confidence: 99%

ApoE gene and exceptional longevity: Insights from three independent cohorts

Garatachea

Emanuele

Calero

et al. 2014

Experimental Gerontology

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This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. The ApoE gene is associated with the risk of Alzheimer or cardiovascular disease but its influence on exceptional longevity (EL) is uncertain. Our primary purpose was to determine, using a case-control design, if the ApoE gene is associated with EL. We compared ApoE allele/genotype frequencies among the following cohorts: cases (centenarians, most with 1 + major disease condition; n = 163, 100-111 years) and healthy controls (n = 1039, 20-85 years) from Spain; disease-free cases (centenarians; n = 79, 100-104 years) and healthy controls (n = 597, age 27-81 years) from Italy; and cases (centenarians and semi-supercentenarians, most with 1+ major disease condition; n = 729, 100-116 years) and healthy controls (n = 498, 23-59 years) from Japan. Our main findings were twofold. First, the ε4-allele was negatively associated with EL in the three cohorts, with the following odds ratio (OR) values (adjusted by sex) having been found: 0.55 (95% confidence interval (CI): 0.33, 0.94), P = 0.030 (Spain); 0.41 (95%CI: 0.18, 0.99), P = 0.05 (Italy); and 0.35 (95%CI: 0.26, 0.57), P b 0.001 (Japan). Second, although no association was found in the Spanish cohort (OR = 1.42 (95%CI: 0.89, 2.26), P = 0.145), the ε2-allele was positively associated with EL in the Italian (OR = 2.14 (95%CI: 1.18, 3.45), P = 0.01) and Japanese subjects (OR = 1.81 (95%CI: 1.25, 2.63), P = 0.002). Notwithstanding the limitations of case-control designs, our data suggest that the ApoE might be a candidate to influence EL. The ε4-allele appears to decrease the likelihood of reaching EL among individuals of different ethnic/geographic origins. An additional, novel finding of our study was that the ε2-allele might favor EL, at least in the Italian and Japanese cohorts.

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“…A second pilot association study utilized six previously described coding polymorphisms within the WRN gene (Meisslitzer et al 1997;Ye et al 1997;Vidal et al 1998;Castro et al 1999). Each of these was used separately in an attempt to establish association between any of the coding SNPs (cSNPs) and the WRN inferred haplotypes.…”

Section: Pilot Association Studiesmentioning

confidence: 99%

“…In some reactions 4%-8% DMSO was added to facilitate the annealing of the primer to the template. Six known coding polymorphisms within the WRN gene (Meisslitzer et al 1997;Ye et al 1997;Vidal et al 1998;Castro et al 1999) were used in an association pilot study. PCR products spanning the polymorphisms were pooled together into two multiplex groups (Supplementary Table 1 available online at http:// www.genome.org.)…”

Section: Snp Identification and Detectionmentioning

confidence: 99%

Complex SNP-Based Haplotypes in Three Human Helicases: Implications for Cancer Association Studies

Trikka

Fang²,

Renwick³

et al. 2002

Genome Res.

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We have initiated a candidate gene approach to study variation and predisposition to cancer in the four major ethnic groups that constitute the U.S. population (African Americans, Caucasians, Hispanics, and Asians). We resequenced portions of three helicase genes (BLM, WRN, and RECQL) identifying a total of 37 noncoding single nucleotide polymorphisms (SNPs). Haplotype inference predicted 50 haplotypes in BLM, 56 in WRN, and 47 in RECQL in a sample of 600 chromosomes. Approximately 10% of the predicted haplotypes were shared among all ethnic groups. Linkage disequilibrium and recombination effects showed that each locus has taken a diverse evolutionary path. Primate DNA analysis of the same loci revealed one human haplotype per gene shared with the great apes, indicating that the observed diversity occurred since the divergence of humans from the last common ancestor. In BLM, we confirmed the presence of a founder haplotype among Ashkenazi Jews homozygous for the blm Ash mutation. The cosegregating haplotype was seen in all (6/6) samples of Ashkenazi descent, whereas in the general population it has a low frequency (0.02) and was not found in African Americans. In WRN, ethnic samples were studied for their haplotype content and the presence or absence of six previously described coding SNPs (cSNPs). Hispanic individuals carrying two of these cSNPs showed a 60% increase in the frequency of a common haplotype (haplotype No. 28). In the pooled sample, no association was found. Because (1) the majority of the haplotypes are population specific and (2) the patterns of linkage disequilibrium, recombination, and haplotype diversity are markedly different between gene regions, these data show the importance of either ethnically matched controls or within-family-based disease-gene association studies.

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Polymorphisms at the Werner locus: I. Newly identified polymorphisms, ethnic variability of 1367Cy/Arg, and its stability in a population of Finnish centenarians

Cited by 67 publications

References 16 publications

Health‐Protective and Adverse Effects of the Apolipoprotein E ɛ2 Allele in Older Men

Health‐Protective and Adverse Effects of the Apolipoprotein E ɛ2 Allele in Older Men

ApoE gene and exceptional longevity: Insights from three independent cohorts

Complex SNP-Based Haplotypes in Three Human Helicases: Implications for Cancer Association Studies

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