Pro12Ala Polymorphism of the PPARγ2 Gene Interacts With a Mediterranean Diet to Prevent Telomere Shortening in the PREDIMED-NAVARRA Randomized Trial

Abstract

Background— The gene variant Pro/Ala (rs1801282) in the PPARγ2 has been associated with lower cardiovascular risk and greater benefit from lifestyle interventions. This polymorphism also seems to be associated with longer lifespan, but no information on telomere length (TL) is available. Our aim was to study the association between the Ala allele and changes in TL in high cardiovascular risk subjects and the potential interaction with a Mediterranean dietary pattern. Methods and Results— A total of 521 subjects (55–80 years) participating in the Prevención con Dieta Mediterránea randomized trial were genotyped. Changes in TL, measured by quantitative real-time polymerase chain reaction (PCR), were assessed over 5 years of a nutritional intervention, which promoted adherence to the Mediterranean diet (MeDiet). Interestingly, Ala carriers showed lower telomere shortening after 5 years compared with the Pro/Pro genotype ( P =0.031). This association was modulated by MeDiet because those Ala carriers who reported better conformity to the MeDiet exhibited increased TL ( P <0.001). Moreover, a reduction in carbohydrate intake (≤9.5 g/d) resulted in increased TL among Ala carriers. Notably, an apparent gene–diet interaction was found through the observed changes in the MUFA+PUFA/carbohydrates ratio: as this ratio increased, TL lengthening was detected to a greater extent in the Ala carriers compared with the Pro/Pro subjects ( P for interaction <0.001). Conclusions— The Pro12Ala polymorphism is associated with TL homeostasis after 5 years follow-up in subjects at high cardiovascular risk. In addition, a higher adherence to the MeDiet pattern strengthens the prevention of telomere shortening among Ala carriers. Clinical Trial Registration— www.controlled-trials.com ; Unique Identifier: ISRCTN35739639.

Oxidative stress, telomeres and cellular senescence: What non-drug interventions might break the link?

“…In this study participants who were given the MD supplemented with olive oil showed no differences in telomere erosion over a five year period when compared to a control group given a low fat diet; unexpectedly, accelerated telomere shortening was observed in participants on the MD supplemented with nuts [75]. Importantly however, the study found that greater adherence to the MD reduced telomere shortening in individuals carrying the Ala variant of the PPARγ2 gene, but not in those carrying the Pro variant [74]. Thus, although the study concluded that overall there was no beneficial effect of the MD intervention on slowing telomere shortening in comparison to a low fat diet, it also highlighted the potential relevance of genetic factors when considering the effects of diets on telomere length.…”

“…The studies were generally small and heterogeneous with respect to the age and health characteristics of the participants, as well as the duration of the interventions. The majority lasted for less than a year [62][63][64][65][66][67][68][69][70][71][72], while four trials were conducted for a year or more [73][74][75][76][77]. In all of them telomere length was determined in either leukocytes or PBMC before and after the intervention.…”

Association of telomere length with IL‐6 levels during an obesity treatment in adolescents: interaction with the‐174G/C polymorphism in the IL‐6gene

“…The T/S ratio was calculated as follows [2 CT(telomeres) /2 CT(single copy gene) ] =2 ‐ΔCT , because the amount of the PCR product approximately doubles in each cycle of the PCR . More detailed information about this method has been published elsewhere …”

“…The T/S ratio was calculated as follows [2 CT(telomeres) /2 CT(single copy gene) ] =2 -ΔCT , because the amount of the PCR product approximately doubles in each cycle of the PCR (21). More detailed information about this method has been published elsewhere (2,3,22) For quality control, all samples were run in triplicate and checked for concordance between triplicate values. In order to achieve a robust consistence, samples showing a high variation (more than 10%) were rerun and reanalysed.…”

Genetic variation in TNFα, PPARγ, and IRS-1 genes, and their association with breast-cancer survival in the HEAL cohort

“…[11–13], and lower rates of telomere shortening compared with the Pro/Pro genotype. [14] Results from studies investigating the association between the Pro 12 Ala polymorphism and breast-cancer risk have been conflicting: some studies reported a marginally increased risk associated with the Ala genotype. [15,16], although others did not.…”