Lipoprotein receptor-related protein 1 variants and dietary fatty acids: meta-analysis of European origin and African American studies
Open accessAbstract
Objective Low-density lipoprotein-related receptor protein 1 (LRP1) is a multi-functional endocytic receptor and signaling molecule that is expressed in adipose and the hypothalamus. Evidence for a role of LRP1 in adiposity is accumulating from animal and in vitro models, but data from human studies are limited. The study objectives were to evaluate (i) relationships between LRP1 genotype and anthropometric traits, and (ii) whether these relationships were modified by dietary fatty acids.Design and methods We conducted race/ethnic-specific meta-analyses using data from 14 studies of US and European whites and 4 of African Americans to evaluate associations of dietary fatty acids and LRP1 genotypes with body mass index (BMI), waist circumference and hip circumference, as well as interactions between dietary fatty acids and LRP1 genotypes. Seven single-nucleotide polymorphisms (SNPs) of LRP1 were evaluated in whites (N up to 42 000) and twelve SNPs in African Americans (N up to 5800).Results After adjustment for age, sex and population substructure if relevant, for each one unit greater intake of percentage of energy from saturated fat (SFA), BMI was 0.104 kg m(-2) greater, waist was 0.305 cm larger and hip was 0.168 cm larger (all P<0.0001). Other fatty acids were not associated with outcomes. The association of SFA with outcomes varied by genotype at rs2306692 (genotyped in four studies of whites), where the magnitude of the association of SFA intake with each outcome was greater per additional copy of the T allele: 0.107 kg m(-2) greater for BMI (interaction P=0.0001), 0.267 cm for waist (interaction P=0.001) and 0.21 cm for hip (interaction P=0.001). No other significant interactions were observed.Conclusion Dietary SFA and LRP1 genotype may interactively influence anthropometric traits. Further exploration of this, and other diet x genotype interactions, may improve understanding of interindividual variability in the relationships of dietary factors with anthropometric traits.
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Evidence for interactions between diet and these genes is uncommon.
“Large investigations pooling multiple cohorts have observed main (population) effects of either dietary influences or genes on major cardiometabolic risk factors, but evidence for interactions between diet and these genes is uncommon and, more relevantly, magnitudes of such potential interactions are often small.78-83”
From Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity: A Comprehensive Review (2016) · cites this paper as [79]
Large investigations pooling multiple cohorts have observed main (population) effects of either dietary influences or genes on major cardiometabolic risk factors.
“Large investigations pooling multiple cohorts have observed main (population) effects of either dietary influences or genes on major cardiometabolic risk factors, but evidence for interactions between diet and these genes is uncommon and, more relevantly, magnitudes of such potential interactions are often small.78-83”
From Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity: A Comprehensive Review (2016) · cites this paper as [79]
Magnitudes of such potential gene-diet interactions are often small.
“Large investigations pooling multiple cohorts have observed main (population) effects of either dietary influences or genes on major cardiometabolic risk factors, but evidence for interactions between diet and these genes is uncommon and, more relevantly, magnitudes of such potential interactions are often small.78-83”
From Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity: A Comprehensive Review (2016) · cites this paper as [79]
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- Authors
- Smith, C. E., Ngwa, J., Tanaka, T., Qi, Q., Wojczynski, M. K., Lemaitre, R. N., Anderson, J. S., Manichaikul, A., Mikkilä, V, van Rooij, F. J. A., Ye, Z., Bandinelli, S., Frazier-Wood, A. C., Houston, D. K., Hu, F., Langenberg, C., McKeown, N. M., Mozaffarian, D., North, K. E., Viikari, J., Zillikens, M. C., Djoussé, L., Hofman, A., Kähönen, M., Kabagambe, E. K., Loos, R. J. F., Saylor, G. B., Forouhi, N. G., Liu, Y., Mukamal, K. J., Chen, Y.-D., Tsai, M. Y., Uitterlinden, A. G., Raitakari, O., van Duijn, C. M., Arnett, D. K., Borecki, I. B., Cupples, L. A., Ferrucci, L., Kritchevsky, S. B., Lehtimäki, T., Qi, L., Rotter, J. I., Siscovick, D. S., Wareham, N. J., Witteman, J. C. M., Ordovás, J. M., & Nettleton, J. A.
- Affiliations
- Tufts University (US)
- Boston University (US)
- National Institute on Aging (US)
- Harvard University (US)
- Washington University in St. Louis (US)
- Wake Forest University Health Sciences (US)
- University of Virginia (US)
- University of Helsinki (FI)
- Addenbrooke's Hospital (GB)
- Azienda Sanitaria di Firenze (IT)
- Brigham and Women's Hospital (US)
- University of North Carolina at Chapel Hill (US)
- University of Turku (FI)
- Erasmus MC (NL)
- Tampere University Hospital (FI)
- University of Alabama at Birmingham (US)
- Beth Israel Deaconess Medical Center (US)
- Cedars-Sinai Medical Center (US)
- University of Minnesota (US)
- University of Washington (US)
- The University of Texas Health Science Center at Houston (US)
- Corresponding author
- Ordovás, J M
- ORCID
- Smith, C E
- Ngwa, J
- Tanaka, T
- Wojczynski, M K
- Manichaikul, A
- Ye, Z
- Bandinelli, S
- Houston, D K
- Langenberg, C
- McKeown, N M
- Mozaffarian, D
- North, K E
- Viikari, J
- Zillikens, M C
- Djoussé, L
- Hofman, A
- Kähönen, M
- Kabagambe, E K
- Loos, R J F
- Forouhi, N G
- Liu, Y
- Mukamal, K J
- Tsai, M Y
- Uitterlinden, A G
- Raitakari, O
- Arnett, D K
- Borecki, I B
- Cupples, L A
- Ferrucci, L
- Kritchevsky, S B
- Lehtimäki, T
- Qi, Lu
- Rotter, J I
- Siscovick, D S
- Wareham, N J
- Ordovás, J M
- Venue
- International Journal of Obesity
- Published
- 2013-01-29
- Volume
- 37
- Issue
- 9
- Pages
- 1211-1220
- ISSN
- 0307-0565 (ISSN-L)
- 1476-5497
- PMC
- PMC3770755
- OpenAlex
- W2018949182
- Cited by
- 10
- References
- 40
- Citations by year
- 2023: 1 · 2019: 1 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 3 · 2013: 1 · 2012: 1
- FWCI
- 0.25
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- International Journal of Obesity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust
- British Heart Foundation
- National Institutes of Health (n01hc95164-17-0-1, 5r01ag032098-05, n01ag062101-007, n01hc045133-001, n01hc085079-024, n01hc015103-009, n01ag062103-006, n01hc95165-34-0-1, 5r01ca049449-18, n01hc95161-24-0-1, n01hc095169-003, n01ag062106-007, UL1TR000124, n01hc95166-21-0-1, n01hc085086-022, 5r01hl087700-03, n01hc95162-31-0-1, n01hc95168-27-0-1, n01hc95160-18-0-1, n01hc095167-000, n01hc25195-41-0-1, n01hc95163-22-0-1, 5r01hl088215-04, n01hc55222-0-0-0, n01hc95159-40-0-1, n01hc075150-004, n01hc035129-010)
- U.S. Public Health Service (HHSN 268200625226C)
- Medical Research Council (MC_UU_12015/5, MC_UU_12015/1)
- National Institute on Aging (R01AG032098, AG 20098, R56AG023629, R01AG020098, P01AG023394, AG023629, N01 AG062106, AG027058, R56AG020098, R01AG023629, R01AG015928, N01 AG062103, R01AG027058, N01 AG062101)
- National Heart, Lung, and Blood Institute (HHSN268201 100012C, HHSN268201100007I, R01HL071205, N01 HC085086, HHSN268201100007C, N01 HC-95159, N01-HC-95160, N01-HC095169, R01-HL-088215, HHSN2682 01100008C, N01 HC-95168, HH-SN-268201100006C, R01HL071252, N0-1-HC-85239, HHSN268201100011C, HL 71981, HHSN2682011-00005I, R01HL085251, R01HL071981, N01 HC95167, HL-105756, N01 HC085079, (N01-HC-95163, N01‐HC25195, HL-087652, R01HL071259, N01HC‐75150, N01 HC85086, HHSN2682011-00009I, R01 HL-59367, N01 HC-95161, N01 HC95165, N01HC95164, R01HL087652, HHSN268201100005C, R01HL071251, N01 HC035129, HHSN268201100005G, HHSN268201100010C, R01-HL087700, N01-HC-095159, N02- HL-64278, U01HL072524, N01 HC015103, N01 HC55222, HHSN268201100011I, R01HL071051, R01HL071250, N01-HC-025195, R01HL087641, HHSN268201200036C, R01HL059367, HHSN26820 1100009C, R01HL105756, U01HL080295, N01 HC055222, HHSN2682011-00008I, N01‐HC‐95166, K08HL112845, R01HL091357, P50HL105185, R01HL071258, HL080295, R01HL080295, N01 HC-95162, N01 HC075150, R01HL117078, N01 HC045133, R01HL086694, N01-HC85079, N01 HC95169)
- National Human Genome Research Institute (U01HG004402, HHSN268200782096C)
- National Cancer Institute (CA-49449, CA-87969, CA055075, P01CA087969, R01‐CA049449, P01CA055075, U01CA049449)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK063491, R01-DK-8925601, R01DK089256, R01DK075681, K01DK082729, P30DK063491)
- National Center for Research Resources (UL1RR024156, UL1RR025005, RR024156)
- National Center for Advancing Translational Sciences
- National Institute on Minority Health and Health Disparities (263MD9164, 263MD 821336, R01MD009164, L60 MD003562)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- LRP1, dietary fatty acids, saturated fat intake, body mass index, waist circumference, hip circumference, anthropometric traits, gene-diet interaction, single nucleotide polymorphisms, adiposity, African Americans
- MeSH terms
- Adipose Tissue, Adult, Aged, Aged, 80 and over, Black or African American, Europe, Fatty Acids, Female, Gene Frequency, Genotype, Humans, Male, Middle Aged, Obesity, Phenotype, United States, Body Mass Index, Prevalence, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Low Density Lipoprotein Receptor-Related Protein-1, Black People, White People, Gene-Environment Interaction
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