Association of telomere length with type 2 diabetes, oxidative stress and UCP2 gene variation
Received 20 February 2009; received in revised form 9 September 2009; accepted 28 September 2009. published online 04 November 2009.
Abstract
Objective
High oxidative stress potentially leads to accelerated telomere shortening and consequent premature cell senescence, implicated in type 2 diabetes (T2D) development. Therefore, we studied the association of leukocyte telomere length (LTL) with the presence of T2D, as well as the effect on the patients’ LTL of plasma oxidative stress and of variation in UCP2, a gene involved in the mitochondrial production of reactive oxygen species.
Methods
Mean LTL was determined in 569 Caucasian, 103 South Asian and 70 Afro-Caribbean T2D patients aged from 24 to 92 years, 81 healthy Caucasian male students aged from 18 to 28 years and 367 healthy Caucasian men aged from 40 to 61 years by real-time PCR. Plasma total antioxidant status (TAOS) was measured in the T2D patients by a photometric microassay. The patients were also genotyped for the UCP2 functional variants −866G>A and A55V.
Results
Afro-Carribeans had 510bp longer mean length compared to Caucasians (p<0.0001) and 500bp longer than South Asians (p=0.004). T2D subjects displayed shorter age-adjusted LTL compared to controls [6.94(6.8–7.03) vs. 7.72(7.53–7.9), p<0.001] with subjects in the middle and the lowest tertile of LTL having significantly higher odds ratios for T2D compared to those in the highest tertile [1.50(1.08–2.07) and 5.04(3.63–6.99), respectively, p<0.0001]. In the patients, LTL was correlated negatively with age (r=−0.18, p<0.0001) and positively with TAOS measures (r=0.12, p=0.01) after adjusting for age, while carriers of the UCP2 −866A allele had shorter age-adjusted LTL than common homozygotes [6.86(6.76–6.96)kb vs. 7.03(6.91–7.15)kb, p=0.04].
Conclusion
The present data suggest that shorter LTL is associated with the presence of T2D and this could be partially attributed to the high oxidative stress in these patients. The association of the UCP2 functional promoter variant with the LTL implies a link between mitochondrial production of reactive oxygen species and shorter telomere length in T2D.
aCentre for Cardiovascular Genetics, Department of Medicine, British Heart Foundation Laboratories, Rayne Building, Royal Free and University College Medical School, 5 University Street, London, WC1E 6JF, UK
bDiabetes Research Group, Institute of Life Sciences, Swansea University, Singleton Park, Swansea, SA2 8PP, UK
ABSTRACT