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


CONCLUSIONS
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.
Zhang
Feng
F
Twin Research and Genetic Epidemiology Unit, St. Thomas' Hospital, King's College London, United Kingdom. feng.zhang@kcl.ac.uk
Kato
Bernet S
BS
Gardner
Jeffery P
JP
Kimura
Masayuki
M
Spector
Tim D
TD
Ahmadi
Kourosh R
KR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005966:Glucuronidase / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D000090265:Klotho Proteins; D007962:Leukocytes / Q000502:physiology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016615:Telomere / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D014429:Twins, Dizygotic; D044465:White People / Q000235:genetics
D053773:Transforming Growth Factor beta1; D005966:Glucuronidase; D000090265:Klotho Proteins