Year: 2012
Type: article
Abstract: BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSION: 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.
Source: PLoS ONE
Institutions: Vanderbilt University, VA Tennessee Valley Healthcare System
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,382
Funders: Dr. Robert C. and Veronica Atkins Foundation, Vanderbilt University, Almond Board of California, Georgia Clinical and Translational Science Alliance, National Institutes of Health, Vanderbilt Diabetes Research and Training Center, Vanderbilt University Medical Center, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources
Awards: G117257630, G1531600799, G1705214422, G1805704937, G1902834443, G2019238319, G2043477120, G2120971582, G2304076072, G2634810823, G2703310063, G334768891, G4378456092, G560889077, G563474107, The Vanderbilt Institute for Clinical and Translational Research (VICTR) KL2, G608544753, Pharmacogenetics of obesity and endocannabinergic modulation (POEM), Diabetes Research and Training Center, G9000043901, G9000052735, G9000129197, G9000300101, Vanderbilt Diabetes Research Center, G949362299
OpenAlex ID: W1968075386