Common variants near TERC are associated with leukocyte telomere length in the Chinese Han population

Abstract

A recent genome-wide association study has identified an association between leukocyte telomere length (LTL) and a locus at 3q26 that includes TERC. In order to evaluate the effects of the SNPs rs12696304 and rs16847897 near TERC in the population of mainland China, we conducted an association study of LTL focusing on these two candidate SNPs in a sample of 4016 Chinese Han individuals. Multiple linear regression analyses were performed to evaluate the association of LTL with each SNP adjusted for age, gender and diabetes status. In the study, we confirmed the association of SNP rs12696304 and rs16847897 near TERC with LTL in the Chinese Han population (PB4.5Â10 À3 and 9.5Â10 À5 , respectively). Each copy of the major allele of rs12696304 and rs16847897 was associated with a shorter mean telomere length of 0.024 and 0.031 T/S respectively, which is equivalent to about 3 and 4 years of average age-related telomere attrition. Our short report confirmed the effects of SNPs near TERC on LTL in the Chinese Han population for the first time. Keywords: Chinese population; TERC; leukocyte telomere length INTRODUCTIONTelomeres are structures at the ends of eukaryotic chromosomes, which are made up of a repetitive sequence and which has a major role in genomic stability. Telomere dysregulation can lead to cell death, cell senescence, or abnormal cell proliferation. 1 In humans, leukocyte telomere length (LTL) is getting shorter progressively with age, and is frequently reported to be relatively shorter in aging-related diseases: such as Alzheimer's disease 2 and vascular dementia. 3 Telomere length varies between individuals of the same age, and is found to be inheritable in quantitative-trait linkage analyses of sib pairs. 4,5 Quantitative trait locus studies have mapped putative loci for telomere length to human chromosomes 3p26.1, 10q26.13, 12q12.22 and 14q23.2. [5][6][7] Telomerase is a large, mainly uncharacterized, RNA-protein complex that is responsible for the de novo synthesis and maintenance of telomere ends. TERC is a main component of telomerase, which serves as a template for addition of multiple 6 bp (TTAGGG) telomere repeats. A recent genome-wide association study (GWAS) identified association of common variants near TERC (on 3q26) with telomere length in two large European cohorts of 2917 individuals, followed by replication in three further European cohorts of 9492 individuals. 8 The strongest associations with LTL were observed for SNP rs12696304 and rs16847897 near TERC on 3q26, and the association signals across the 3q26 locus between rs12696304 and rs16847897 are located toward opposite ends of an B87 kb region showing significant

Telomere Length and Aging

“…Prescott et al replicated previously identified GWAS loci TERC in the Nurses' Health Study but failed to replicate other locus or identify any new loci significant associated with Telomere Length . Shen et al, not surprisingly detected the TERC locus to have significant effect on Leukocyte Telomere Length in Chinese population through unbiased genome screening (Shen et al, 2011); the same two SNPs were found to be associated with Telomere Length as well as longevity in the oldest-old Danes (Soerensen et al, 2011).…”

Evolutionary conserved longevity genes and human cognitive abilities in elderly cohorts

“…In the first instance, the significance threshold was determined by the Bonferroni method, which corrects the critical significance level by the number of tests (n) performed (a¼0.05/n), and is commonly used in candidate gene studies. 41 It is recognized that the Bonferroni correction can be overly conservative for non-independent tests. 42 Therefore, we calculated the number of independent tests performed.…”

Meta-analysis of telomere length in 19 713 subjects reveals high heritability, stronger maternal inheritance and a paternal age effect

“…11 Genetic association studies have revealed associations between single-nucleotide polymorphisms (SNPs) in the TERC and TERT genes and TL. [11][12][13][14][15][16][17] Other studies reported associations between SNPs in TERC and POT1 with human longevity, 11,17,18 suggesting that genes regulating TL may influence human longevity.…”