Interaction between a variant of CDKN2A/B-gene with lifestyle factors in determining dyslipidemia and estimated cardiovascular risk: A step toward personalized nutrition.

Background & Aims: Several genome-wide-association-studies have identified genetic variants in a region on chromosome 9p21 that are associated with an increased risk of Cardiovascular disease (CVD) and diabetes. Here we have explored the interaction of a genetic variant of the CDKN2A/B-rs10811661 gene locus with cardiovascular risk factors and environmental-exposures (e.g., diet and physical activity) in 1165 individuals recruited from the Mashhad-Stroke and Heart-Atherosclerotic-Disorders cohort.

Methods: Genotyping was carried out using TaqMan-real-time-PCR based method. The association of CDKN2A/B-rs10811661 locus and its interaction with dietary intake in association with the main determinants of dyslipidemia, and cardiovascular-risk-factors were assessed in 2 cohorts.

Results: Our data showed that obese subjects with a TT genotype had a higher level of TG, TG/HDL ratio and Hs-CRP, compared to the subjects with the wild type genotype, or individuals with a normal BMI. Moreover, the presence of a TT genotype was associated with increased risk of hypercholesterolemia, insulin resistance and CVD. These effects were more pronounced in the sub-group with low physical activity and a high dietary energy intake (e.g., the interaction between TT genotype and total energy intake on serum cholesterol was positive (RERI: 0.2, 95%CI (-0.96-1.3), AP: 0.1, 95%CI (-0.5-0.7) and SI: 1.2, 95%CI (0.3-5.1))).

Conclusions: We have found a significant association between the CDKN2A-rs10811661 polymorphism with cardiovascular risk factors and dyslipidemia in a non-diabetic population. It is possible that a low energy diet and high physical activity could ameliorate the unfavorable effects of T allele of CDKN2A/B locus. Functional analysis is warranted to investigate the value of this genetic biomarker of CVD risk in obese people.