Author/Editor		Černe, Jasmina Živa; Pohar Perme, Maja; Cerkovnik, Petra; Geršak, Ksenija; Novaković, Srdjan
Title		Functional variants in CYP1B1, KRAS and MTHFR genes are associated with shorter telomere length in postmenopausal women
Type		članek
Vol. and No.		Letnik 149, št. Vol. 149
Publication year		2015
Volume		str. 1-7
ISSN		1872-6216 - Mechanisms of ageing and development
Language		eng
Abstract		Estrogens and antioxidants indirectly alleviate telomere attrition. However, available clinical data on the association between hormone exposure and telomere length are inconclusive. In the present study, we examined the effects of exogenous estrogen use and of some genetic factors implicated in estrogen metabolism and oxidative stress response on mean leukocyte telomere length. We studied 259 postmenopausal women. Genotyping was conducted for CYP1B1 (rs1056836), COMT (rs4680), GSTP1 (rs1695), MnSOD (rs4880), KRAS (rs61764370), and MTHFR (rs1801133 and rs1801131) polymorphisms. Mean leukocyte telomere length was measured using a quantitative real-time PCR assay. In multivariate analysis we found no association between oral contraceptives or hormone replacement therapy (HRT) and mean leukocyte telomere length. The presence of variant alleles in CYP1B1, KRAS and MTHFR genes was statistically significantly associated with shorter mean leukocyte telomere length. Further, the data provided evidence for the effect modification of the association between HRT and mean leukocyte telomere length by the CYP1B1, KRAS and MTHFR genotypes. Our findings suggest that functionally relevant genetic variants within estrogen and folate metabolic pathways may influence telomere length. We propose these genetic factors should be taken into consideration when interpreting associations between hormone exposure and telomere length.
Keywords		dolžina telomere hormonska nadomestna terapija pomenopavza estrogeni metabolizem telomere length hormone replacement therapy estrogen metabolism postmenopause