Association ofTERTpolymorphisms and risk of coronary heart disease in a Chinese Han population

Abstract

Genome-wide association studies have identified that TERT gene was associated with telomere length and age-related diseases. However, little study directly focused on the association between TERT gene polymorphisms and risk of coronary heart disease (CHD). We conducted a case-control study to examine the effect of TERT polymorphisms on CHD risk among 596 CHD patients and 603 healthy controls from China. Five significant single nucleotide polymorphisms (SNP) in TERT were selected and genotyped using Sequenom Mass-ARRAY technology. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression adjusting for age and gender. Allelic model analysis revealed that for TERT rs10069690, allele frequency distributions differed between cases and controls (OR= 1.267, 95%CI = 1.018-1.576; p = 0.034). Genotypic model analysis revealed that genotype frequency distributions of rs10069690 differed between cases and controls after adjusted by age and sex (TC vs. CC: adjusted OR = 1.352, 95% CI = 1.007-1.815; p = 0.045). Genetic model analysis revealed that rs10069690 was associated with an increased risk of CHD under co-dominant, dominant, over-dominant and log-additive models. After adjustments, it remained significant under over-dominant model (adjusted OR = 1.35, 95% CI = 1.01-1.81; p = 0.044). Our results shed new light on the association between telomere-related gene TERT polymorphisms and CHD susceptibility in a Chinese Han population.

Germline risk of clonal haematopoiesis

“… Locus associated with mLOY? Associations between germline variation in gene and diseases of ageing Associations between somatic gene changes and diseases of ageing TERT Yes Yes Yes Cancer 164 ; CVD 165 – 167 ; dementia 178 Cancer 179 ; CVD 180 ; dementia 181 , 182 CHEK2 Yes Yes Yes Cancer 120 – 124 Cancer 183 ATM Yes Yes Yes Cancer 133 – 138 Cancer 184 TCL1A Yes Yes Yes NA Cancer 185 46/1 haplotype Yes Yes No Cancer 82 – 84 NA SH2B3 Yes Yes No Cancer 144 ; CVD 153 – 157 Cancer 144 TET2 Yes No Yes Cancer 141 – 143 ; CVD 148 Cancer 186 ; CVD 50 , 51 , 54 , 56 , 147 MAD1L1 …”

“…Recent work using Mendelian randomization has suggested that the telomere–CH relationship is actually bidirectional: longer telomeres may partly cause CHIP (perhaps through an increased propensity for mutation) whereas CHIP, once acquired, may contribute to telomere shortening (possibly via increased rates of cell cycling) 163 . Importantly, genetic association studies of telomere maintenance genes have revealed links to a broad spectrum of diseases, including strong ties to cancer 164 and CVD 165 – 168 . Future work investigating links between telomere length and these diseases (or CH and these diseases) may need to account for mediating effects through the telomere–CH axis.…”

Single Nucleotide Polymorphisms Related to Telomere Length Predispose for Coronary Heart Disease in Chinese Han Population

“…Our results show that the minor alleles "T" of rs10069690 was associated with a reduced risk of CHD in Han Chinese population. Hongmei H et al [33] showed that the minor allele T of rs10069690 was associated with an increased risk of CHD in some genetic models. We considered that the difference in our ndings from their study can be attributed to sample size, gender and regional difference in the study population.…”

Association of TERT polymorphisms with chronic hepatitis B in a Chinese Han population

“…Recently, it was reported that the T allele of rs10069690 was associated with an increased risk of breast cancer [ 12 ], lung cancer [ 19 ], esophageal cancer [ 23 ], gastric cancer [ 25 ], coronary heart disease [ 26 ]. However, rs10069690 was found to be associated with significantly reduced risk of hepatocellular carcinoma, prostate cancer [ 27 ].…”