Molecular Medicine Group, Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Molecular Medicine Group, Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Biotechnology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran.
Clin Nutr. 2018 Feb;37(1):254-261. doi: 10.1016/j.clnu.2016.12.018. Epub 2016 Dec 28.
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.
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.
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))).
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.
几项全基因组关联研究已经确定了染色体 9p21 上一个区域的遗传变异与心血管疾病（CVD）和糖尿病的风险增加有关。在这里，我们探索了 CDKN2A/B-rs10811661 基因座的遗传变异与 1165 名来自马什哈德中风和心脏动脉粥样硬化疾病队列的个体的心血管危险因素和环境暴露（如饮食和体育活动）之间的相互作用。
使用 TaqMan 实时-PCR 基于方法进行基因分型。在 2 个队列中评估了 CDKN2A/B-rs10811661 基因座与饮食摄入的关联及其与血脂异常的主要决定因素和心血管危险因素的相互作用。
我们的数据表明，与野生型基因型或 BMI 正常的个体相比，TT 基因型的肥胖个体的 TG、TG/HDL 比值和 Hs-CRP 水平更高。此外，TT 基因型与高胆固醇血症、胰岛素抵抗和 CVD 风险增加有关。这些影响在低体力活动和高饮食能量摄入的亚组中更为明显（例如，TT 基因型与血清胆固醇总能量摄入之间的相互作用为正（RERI：0.2，95%CI（-0.96-1.3），AP：0.1，95%CI（-0.5-0.7），SI：1.2，95%CI（0.3-5.1）））。
我们在非糖尿病人群中发现 CDKN2A-rs10811661 多态性与心血管危险因素和血脂异常之间存在显著关联。低能量饮食和高体力活动可能会减轻 CDKN2A/B 基因座 T 等位基因的不利影响。需要进行功能分析以研究该遗传生物标志物在肥胖人群中对 CVD 风险的价值。
