Low risk for coronary artery disease and findings in the TERC region on 3q26 - Elizabeth Corder
The TERC region on chromosome 3q26 was investigated for British coronary artery disease patients (n=1487) and for UK blood service donors (n=1430). The aim was to identify region-wide patterns associated with telomere length and their prevalence in the two subject groups. The 131 SNPs distributed over 200,000 bp were represented by 41 variables, either SNP genotype or multilocus genotype for highly correlated SNPs; quantile of leucocyte telomere length (T/S ratio adjusted for age and sex) was used in model estimation. Maximum likelihood was employed to identify region-wide patterns associated with telomere length (fuzzy latent classification; GoM). Three essentially identical region-wide patterns labeled as I, II and III were identified in both samples. Mean adjusted telomere length was 1.84 (n=398), 2.03 (n=148), and 1.85 (n=325) for blood donors who genetically matched the respective patterns, 1.59 (n=369), 1.67 (n=46) and 1.60 (n=321) for the heart patients. Few heart patients matched favorable pattern II (3% vs 10%, p < 0.001), implying protection for coronary heart disease. However, these patients had only marginally longer telomeres as compared to other patients, implying that telomere attrition itself is relevant to coronary artery disease. Considering raw unadjusted T/S found for blood donors who matched one of the patterns, the rate of age-related attrition was small ~20 bp annually for I, II and III. Instead, extrapolating back to birth in linear models, there were large differences in telomere set point: 1.836 (~7840 bp) for pattern I, 2.089 (~8920 bp) for pattern II, and, 1.802 (~7695 bp) for pattern III. We conclude that a specific genetic pattern in the TERC region found for ~10% of the British population predisposes to good health and longevity. The alterations in LRRIQ4 and LRRC31 specific to pattern II are of great interest.