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Lack of association between leukocyte telomere length and genetic variants in two ageing-related candidate genes.

Zhang, F, Kato, BS, Gardner, JP, Kimura, M, Spector, TD and Ahmadi, KR (2007) Lack of association between leukocyte telomere length and genetic variants in two ageing-related candidate genes. Mech Ageing Dev, 128 (7-8). pp. 415-422.

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BACKGROUND: Leukocyte telomere length, a putative marker of ageing, is a highly variable and heritable complex trait. In order to determine the possible underlying genetic variants for leukocyte telomere length variation, we conducted an association study of leukocyte telomere length and two candidate genes for ageing-related traits, TGFB1 and KLOTHO, in a female Caucasian dizygotic twin population. METHODS AND MATERIALS: Terminal restriction fragment (TRF) length, an index of telomere length, was measured using Southern Blotting. Six and four single nucleotide polymorphisms (SNP) were genotyped in TGFB1 and KLOTHO gene, respectively, and tested for association. When there is strong LD between SNPs (r(2) > 0.5), haplotypic association was investigated using haplotype trend regression approach. RESULTS: All SNPs were in Hardy-Weinberg equilibrium (p > 0.05). No significant association was detected for individual SNPs (p > 0.101), or two-locus haplotypes (p = 0.7497) with TRF variation. CONCLUSION: We failed to find any significant association between leukocyte telomere length and 10 SNPs in two ageing-related candidate genes, TGFB1 and KLOTHO. This result suggests that while we could not exclude minor effects, none of 10 SNPs in these two candidate genes showed significant association with the variation of leukocyte telomere length in our cohort. But as it is unclear whether telomere length dynamics is the cause or the effect of the ageing process, it is still possible the genes are associated with ageing via alternate mechanisms.

Item Type: Article
Divisions : Surrey research (other units)
Authors :
Zhang, F
Kato, BS
Gardner, JP
Kimura, M
Spector, TD
Date : July 2007
DOI : 10.1016/j.mad.2007.05.007
Uncontrolled Keywords : Adolescent, Adult, Aged, Aging, European Continental Ancestry Group, Female, Genetic Variation, Glucuronidase, Haplotypes, Humans, Leukocytes, Middle Aged, Polymorphism, Single Nucleotide, Telomere, Transforming Growth Factor beta1, Twins, Dizygotic
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 09:48
Last Modified : 24 Jan 2020 17:42

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