Weight gain prevention buffers the impact of CETP rs3764261 on high density lipoprotein cholesterol in young adulthood: the Study of Novel Approaches to Weight Gain Prevention (SNAP)

Authors: MCCAFFERY, JEANNE - University Of Connecticut; ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; HUGGINS, GORDON - Tufts Medical Center; Lai, Chao Qiang; ESPELAND, MARK - Wake Forest University; TATE, DEBORAH - University Of North Carolina; WING, RENA - Brown University

Submitted to: Nutrition Metabolism and Cardiovascular Disease
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/27/2018
Publication Date: 3/6/2018
Citation: McCaffery, J.M., Ordovas, J.M., Huggins, G.S., Lai, C., Espeland, M.A., Tate, D.F., Wing, R.R. 2018. Weight gain prevention buffers the impact of CETP rs3764261 on high density lipoprotein cholesterol in young adulthood: the Study of Novel Approaches to Weight Gain Prevention (SNAP). Nutrition Metabolism and Cardiovascular Disease. 28(8):816-821. https://doi.org/10.1016/j.numecd.2018.02.018.
DOI: https://doi.org/10.1016/j.numecd.2018.02.018

Interpretive Summary: Two weight gain prevention strategies, one targeting small changes to diet and physical activity and a second targeting large changes, significantly reduced weight gain in young adults. The objective of this study was to examine whether these weight gain prevention interventions blunt genetic risk for body weight increases and/or high-density lipoprotein cholesterol (HDL-C) lowering over two years. Our findings show that participants who carry a common variant in the Cholesteryl ester transfer protein (CETP) gene increased their HDL levels following both weight gain prevention strategies after a small or large amount of food reduction and increased physical activity. The finding provides scientific basis and motivation for those with this CETP genetic variant to lose weight while at the same time improving their cardiovascular risk profile.

Technical Abstract: Background and Aims: Two weight gain prevention strategies, one targeting small changes to diet and physical activity and a second targeting large changes, significantly reduced weight gain in young adulthood. We examined whether weight gain prevention blunts genetic risk for body weight increase and/or high density lipoprotein cholesterol (HDL-C) lowering over two years. Methods and Results: Participants were 524 male and female young adults (mean age = 28.2, SD = 4.3; mean BMI = 25.5, SD = 2.6). Obesity-related SNPs accounting for >/= 0.04% of the variance were genotyped and combined into a genetic risk score. For HDL-C, SNPs within CETP, LIPC and FADS2 were genotyped. The obesity-related genetic risk score did not predict change in BMI independently or in interaction with treatment arm. However, consistent with the prior literature, each copy of the HDL-C risk, C, allele at CETP rs3764261 was associated with lower HDL-C at baseline. Moreover, significant interaction between SNP and treatment arm for change in HDL-C was observed (p = 0.02). In the control group, HDL-C change was dependent upon rs3764261 (p = 0.004) with C allele carriers showing a continued reduction in HDL-C. In contrast, within the two intervention groups, HDL-C increased on average with no differential effect of rs3764261 (p > 0.24). Notably, even among carriers of the CC genotype, small and large change arms were associated with increased HDL-C and the control arm a reduction (p = 0.013). Conclusions: The C allele at CETP rs3764261 is a strong risk factor for low HDL-C in young adulthood but weight gain prevention may mitigate this risk.