Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
PLoS One. 2012;7(5):e36166. doi: 10.1371/journal.pone.0036166. Epub 2012 May 2.
Success in further reducing the burden of cardiovascular disease (CVD) is threatened by the increasing prevalence of obesity-related atherogenic dyslipidemia. HDL-cholesterol (HDL-C) level is inversely correlated with CVD risk; each 1 mg/dl decrease in HDL-C is associated with a 6% reduction in risk. We previously showed that a common CNR1 haplotype, H3 (frequency 20%), is protective against the reduction in HDL-C that typically accompanies weight gain. In the present study, we extend that observation by reporting the effect of CNR1 haplotype on HDL-C response to modification of dietary fat intake in weight maintenance and weight loss.
Six haplotype tagging SNPs that cover the CNR1 gene locus were genotyped in 590 adults of varying body mass index (cohort 1 is 411 males with BMI 18.5-30.0 kg/m(2); cohort 2 is 71 females with BMI18.5-30.0 kg/m(2); and cohort 3 is 108 females with BMI 30-39.9 kg/m(2)). Dietary intakes were modified so that fat intake in the "high fat" condition was 15-20% greater than in the "low fat" condition, and lipid profiles were compared between carriers versus noncarriers for each of the five commonly observed CNR1 haplotypes (H1-H5).
In normal to overweight subjects on eucaloric diets, the H3 haplotype was significantly associated with short-term high fat diet induced changes in HDL-C level in females (carriers 5.9 mg/dl>noncarriers, p = 0.007). The H3 haplotype was also significantly associated with HDL-C level after 16 weeks on high fat calorie restricted diet in obese females (carriers 6.8 mg/dl>noncarriers, p = 0.009).
Variability within the CNR1 gene locus contributes to gender-related differences in the HDL-cholesterol response to change in dietary fat intake. Functional characterization of this relationship in vitro may offer insights that potentially yield therapeutic guidance targeting dietary macronutrient composition, a direction much needed in the current epidemic of obesity.
心血管疾病（CVD）负担的进一步降低受到肥胖相关致动脉粥样硬化性血脂异常患病率增加的威胁。高密度脂蛋白胆固醇（HDL-C）水平与 CVD 风险呈负相关；HDL-C 每降低 1mg/dl，风险降低 6%。我们之前的研究表明，CNR1 常见单倍型 H3（频率 20%）可预防体重增加时通常伴随的 HDL-C 降低。在本研究中，我们通过报告 CNR1 单倍型对饮食脂肪摄入改变时体重维持和减轻体重期间 HDL-C 反应的影响来扩展该观察结果。
在不同体重指数的 590 名成年人（队列 1 为 411 名 BMI 为 18.5-30.0kg/m2 的男性；队列 2 为 71 名 BMI 为 18.5-30.0kg/m2 的女性；队列 3 为 108 名 BMI 为 30-39.9kg/m2 的女性）中，对六个覆盖 CNR1 基因座的单倍型标记 SNP 进行了基因分型。饮食摄入进行了调整，使“高脂肪”条件下的脂肪摄入量比“低脂肪”条件下增加 15-20%，并比较了每个单倍型（H1-H5）在携带者和非携带者之间的五个常见 CNR1 单倍型（H1-H5）的脂质谱。
在正常至超重的热量摄入饮食受试者中，H3 单倍型与女性短期高脂肪饮食诱导的 HDL-C 水平变化显著相关（携带者 5.9mg/dl>非携带者，p=0.007）。H3 单倍型在肥胖女性高脂肪热量限制饮食 16 周后与 HDL-C 水平也显著相关（携带者 6.8mg/dl>非携带者，p=0.009）。
CNR1 基因座内的变异性导致性别相关的 HDL-胆固醇对饮食脂肪摄入变化的反应存在差异。体外对这种关系的功能特征描述可能提供潜在的治疗指导，以针对饮食宏量营养素组成，这在肥胖流行的当前是非常需要的方向。
