@article {6281, title = {Lipoprotein receptor-related protein 1 variants and dietary fatty acids: meta-analysis of European origin and African American studies.}, journal = {Int J Obes (Lond)}, volume = {37}, year = {2013}, month = {2013 Sep}, pages = {1211-20}, abstract = {

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.

}, keywords = {Adipose Tissue, Adult, African Continental Ancestry Group, Aged, Aged, 80 and over, Body Mass Index, Europe, European Continental Ancestry Group, Fatty Acids, Female, Gene Frequency, Gene-Environment Interaction, Genetic Predisposition to Disease, Genotype, Humans, Low Density Lipoprotein Receptor-Related Protein-1, Male, Middle Aged, Obesity, Phenotype, Polymorphism, Single Nucleotide, Prevalence, United States}, issn = {1476-5497}, doi = {10.1038/ijo.2012.215}, author = {Smith, C E and Ngwa, J and Tanaka, T and Qi, Q and Wojczynski, M K and Lemaitre, R N and Anderson, J S and Manichaikul, A and Mikkil{\"a}, V and van Rooij, F J A and Ye, Z and Bandinelli, S and Frazier-Wood, A C and Houston, D K and Hu, F and Langenberg, C and McKeown, N M and Mozaffarian, D and North, K E and Viikari, J and Zillikens, M C and Djouss{\'e}, L and Hofman, A and K{\"a}h{\"o}nen, M and Kabagambe, E K and Loos, R J F and Saylor, G B and Forouhi, N G and Liu, Y and Mukamal, K J and Chen, Y-D I and Tsai, M Y and Uitterlinden, A G and Raitakari, O and van Duijn, C M and Arnett, D K and Borecki, I B and Cupples, L A and Ferrucci, L and Kritchevsky, S B and Lehtim{\"a}ki, T and Qi, Lu and Rotter, J I and Siscovick, D S and Wareham, N J and Witteman, J C M and Ordov{\'a}s, J M and Nettleton, J A} } @article {8260, title = {Genome-wide meta-analysis of variant-by-diuretic interactions as modulators of lipid traits in persons of European and African ancestry.}, journal = {Pharmacogenomics J}, year = {2019}, month = {2019 Dec 06}, abstract = {

Hypertension (HTN) is a significant risk factor for cardiovascular morbidity and mortality. Metabolic abnormalities, including adverse cholesterol and triglycerides (TG) profiles, are frequent comorbid findings with HTN and contribute to cardiovascular disease. Diuretics, which are used to treat HTN and heart failure, have been associated with worsening of fasting lipid concentrations. Genome-wide meta-analyses with 39,710 European-ancestry (EA) individuals and 9925 African-ancestry (AA) individuals were performed to identify genetic variants that modify the effect of loop or thiazide diuretic use on blood lipid concentrations. Both longitudinal and cross sectional data were used to compute cohort-specific interaction results, which were then combined through meta-analysis in each ancestry. These ancestry-specific results were further combined through trans-ancestry meta-analysis. Analysis of EA data identified two genome-wide significant (p < 5 {\texttimes} 10) loci with single nucleotide variant (SNV)-loop diuretic interaction on TG concentrations (including COL11A1). Analysis of AA data identified one genome-wide significant locus adjacent to BMP2 with SNV-loop diuretic interaction on TG concentrations. Trans-ancestry analysis strengthened evidence of association for SNV-loop diuretic interaction at two loci (KIAA1217 and BAALC). There were few significant SNV-thiazide diuretic interaction associations on TG concentrations and for either diuretic on cholesterol concentrations. Several promising loci were identified that may implicate biologic pathways that contribute to adverse metabolic side effects from diuretic therapy.

}, issn = {1473-1150}, doi = {10.1038/s41397-019-0132-y}, author = {de Las Fuentes, L and Sung, Y J and Sitlani, C M and Avery, C L and Bartz, T M and Keyser, C de and Evans, D S and Li, X and Musani, S K and Ruiter, R and Smith, A V and Sun, F and Trompet, S and Xu, H and Arnett, D K and Bis, J C and Broeckel, U and Busch, E L and Chen, Y-D I and Correa, A and Cummings, S R and Floyd, J S and Ford, I and Guo, X and Harris, T B and Ikram, M A and Lange, L and Launer, L J and Reiner, A P and Schwander, K and Smith, N L and Sotoodehnia, N and Stewart, J D and Stott, D J and St{\"u}rmer, T and Taylor, K D and Uitterlinden, A and Vasan, R S and Wiggins, K L and Cupples, L A and Gudnason, V and Heckbert, S R and Jukema, J W and Liu, Y and Psaty, B M and Rao, D C and Rotter, J I and Stricker, B and Wilson, J G and Whitsel, E A} }