Homocysteine levels and leukocyte telomere length

TY - JOUR

T1 - Homocysteine levels and leukocyte telomere length

AU - Richards, J. B.

AU - Valdes, A. M.

AU - Gardner, J. P.

AU - Kato, B. S.

AU - Siva, A.

AU - Kimura, M.

AU - Lu, X.

AU - Brown, M. J.

AU - Aviv, A.

AU - Spector, T. D.

PY - 2008/10

Y1 - 2008/10

N2 - Objective: Elevated plasma homocysteine is a risk factor for vascular diseases, possibly due to homocysteine-mediated increase in oxidative stress and inflammation. As leukocyte telomere length (LTL) registers the cumulative oxidative stress and inflammation, we examined the relationship between homocysteine and LTL. Method: LTL was measured Using the Southern blot method. The relationship between LTL and homocysteine levels was considered for confounding with the following covariates: age, sex, smoking, obesity, physical activity, menopause, hormone replacement therapy use and creatinine clearance. Results: 1,319 healthy subjects were recruited from a population-based cohort. LTL was negatively correlated with plasma homocysteine levels, after adjustment for smoking, obesity, physical activity, menopause, hormone replacement therapy use and creatinine clearance. The difference in multiply-adjusted LTL between the highest and lowest tertile of homocysteine levels was I I I base pairs (p = 0.004), corresponding to 6.0 years of telomeric aging. This relationship was further accentuated by decreased concentrations of serum folate and increased levels of C-reactive protein. Conclusions: Increased homocysteine levels are associated with shortened LTL, further supporting the tenet that LTL is an index of cardiovascular risk. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

AB - Objective: Elevated plasma homocysteine is a risk factor for vascular diseases, possibly due to homocysteine-mediated increase in oxidative stress and inflammation. As leukocyte telomere length (LTL) registers the cumulative oxidative stress and inflammation, we examined the relationship between homocysteine and LTL. Method: LTL was measured Using the Southern blot method. The relationship between LTL and homocysteine levels was considered for confounding with the following covariates: age, sex, smoking, obesity, physical activity, menopause, hormone replacement therapy use and creatinine clearance. Results: 1,319 healthy subjects were recruited from a population-based cohort. LTL was negatively correlated with plasma homocysteine levels, after adjustment for smoking, obesity, physical activity, menopause, hormone replacement therapy use and creatinine clearance. The difference in multiply-adjusted LTL between the highest and lowest tertile of homocysteine levels was I I I base pairs (p = 0.004), corresponding to 6.0 years of telomeric aging. This relationship was further accentuated by decreased concentrations of serum folate and increased levels of C-reactive protein. Conclusions: Increased homocysteine levels are associated with shortened LTL, further supporting the tenet that LTL is an index of cardiovascular risk. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

U2 - 10.1016/j.atherosclerosis.2007.12.035

DO - 10.1016/j.atherosclerosis.2007.12.035

M3 - Article

VL - 200

SP - 271

EP - 277

JO - Atherosclerosis

JF - Atherosclerosis

IS - 2

ER -