Study of effect modifiers of genetically predicted CETP reduction.
CETP
drug target validation
effect modification
precision medicine
Journal
Genetic epidemiology
ISSN: 1098-2272
Titre abrégé: Genet Epidemiol
Pays: United States
ID NLM: 8411723
Informations de publication
Date de publication:
03 2023
03 2023
Historique:
revised:
11
11
2022
received:
26
07
2022
accepted:
11
01
2023
pubmed:
27
1
2023
medline:
3
3
2023
entrez:
26
1
2023
Statut:
ppublish
Résumé
Genetic variants in drug targets can be used to predict the long-term, on-target effect of drugs. Here, we extend this principle to assess how sex and body mass index may modify the effect of genetically predicted lower CETP levels on biomarkers and cardiovascular outcomes. We found sex and body mass index (BMI) to be modifiers of the association between genetically predicted lower CETP and lipid biomarkers in UK Biobank participants. Female sex and lower BMI were associated with higher high-density lipoprotein cholesterol and lower low-density lipoprotein cholesterol for the same genetically predicted reduction in CETP concentration. We found that sex also modulated the effect of genetically lower CETP on cholesterol efflux capacity in samples from the Montreal Heart Institute Biobank. However, these modifying effects did not extend to sex differences in cardiovascular outcomes in our data. Our results provide insight into the clinical effects of CETP inhibitors in the presence of effect modification based on genetic data. The approach can support precision medicine applications and help assess the external validity of clinical trials.
Substances chimiques
Cholesterol Ester Transfer Proteins
0
Cholesterol, HDL
0
Cholesterol, LDL
0
Biomarkers
0
CETP protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
198-212Subventions
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Organisme : CIHR
ID : 162307
Pays : Canada
Informations de copyright
© 2023 The Authors. Genetic Epidemiology published by Wiley Periodicals LLC.
Références
Anagnostopoulou, K. K., Kolovou, G. D., Kostakou, P. M., Mihas, C., Hatzigeorgiou, G., Marvaki, C., Degiannis, D., Mikhailidis, D. P., & Cokkinos, D. V. (2009). Sex-associated effect of CETP and LPL polymorphisms on postprandial lipids in familial hypercholesterolaemia. Lipids in health and disease, 8, 24. https://doi.org/10.1186/1476-511X-8-24
Arai, H., Teramoto, T., Daida, H., Ikewaki, K., Maeda, Y., Nakagomi, M., Shirakawa, M., Kakikawa, T., Numaguchi, H., Johnson-Levonas, A. O., Vaidya, S., & Blaustein, R. O. (2016). Efficacy and safety of the cholesteryl ester transfer protein inhibitor anacetrapib in Japanese patients with heterozygous familial hypercholesterolemia. Atherosclerosis, 249, 215-223. https://doi.org/10.1016/j.atherosclerosis.2016.03.017
Arsenault, B. J., Petrides, F., Tabet, F., Bao, W., Hovingh, G. K., Boekholdt, S. M., Ramin-Mangata, S., Meilhac, O., DeMicco, D., Rye, K.-A., Waters, D. D., Kastelein, J. J. P., Barter, P., & Lambert, G. (2018). Effect of atorvastatin, cholesterol ester transfer protein inhibition, and diabetes mellitus on circulating proprotein subtilisin kexin type 9 and lipoprotein(a) levels in patients at high cardiovascular risk. Journal of Clinical Lipidology, 12(1), 130-136. https://doi.org/10.1016/j.jacl.2017.10.001
Blauw, L. L., Li-Gao, R., Noordam, R., de Mutsert, R., Trompet, S., Berbée, J., Wang, Y., van Klinken, J. B., Christen, T., van Heemst, D., Mook-Kanamori, D. O., Rosendaal, F. R., Jukema, J. W., Rensen, P., & Willems van Dijk, K. (2018). CETP (cholesteryl ester transfer protein) concentration: A genome-wide association study followed by mendelian randomization on coronary artery disease. Circulation. Genomic and precision medicine, 11(5), 002034. https://doi.org/10.1161/CIRCGEN.117.002034
Blauw, L. L., de Mutsert, R., Lamb, H. J., de Roos, A., Rosendaal, F. R., Jukema, J. W., Wang, Y., van Dijk, K. W., & Rensen, P. C. N. (2016). Serum CETP concentration is not associated with measures of body fat: The NEO study. Atherosclerosis, 246, 267-273. https://doi.org/10.1016/j.atherosclerosis.2016.01.031
Blauw, L. L., Noordam, R., Soidinsalo, S., Blauw, C. A., Li-Gao, R., de Mutsert, R., Berbée, J. F. P., Wang, Y., van Heemst, D., Rosendaal, F. R., Jukema, J. W., Mook-Kanamori, D. O., Würtz, P., Willems van Dijk, K., & Rensen, P. C. N. (2019). Mendelian randomization reveals unexpected effects of CETP on the lipoprotein profile. European Journal of Human Genetics, 27(3), 422-431. https://doi.org/10.1038/s41431-018-0301-5
Bloomfield, D., Carlson, G. L., Sapre, A., Tribble, D., McKenney, J. M., Littlejohn, T. W., 3rd, Sisk, C. M., Mitchel, Y., & Pasternak, R. C. (2009). Efficacy and safety of the cholesteryl ester transfer protein inhibitor anacetrapib as monotherapy and coadministered with atorvastatin in dyslipidemic patients. American Heart Journal, 157(2), 352-360. https://doi.org/10.1016/j.ahj.2008.09.022
Burgess, S., Ference, B. A., Staley, J. R., Freitag, D. F., Mason, A. M., Nielsen, S. F., Willeit, P., Young, R., Surendran, P., Karthikeyan, S., Bolton, T. R., Peters, J. E., Kamstrup, P. R., Tybjaerg-Hansen, A., Benn, M., Langsted, A., Schnohr, P., Vedel-Krogh, S., Kobylecki, C. J., … European Prospective Investigation Into Cancer and Nutrition-Cardiovascular Disease (EPIC-CVD) Consortium. (2018). Association of LPA variants with risk of coronary disease and the implications for lipoprotein(a)-lowering therapies: A mendelian randomization analysis. JAMA Cardiology, 3(7), 619-627. https://doi.org/10.1001/jamacardio.2018.1470
Burgess, S., Freitag, D. F., Khan, H., Gorman, D. N., & Thompson, S. G. (2014). Using multivariable Mendelian randomization to disentangle the causal effects of lipid fractions. PLoS One, 9(10), e108891. https://doi.org/10.1371/journal.pone.0108891
Bycroft, C., Freeman, C., Petkova, D., Band, G., Elliott, L. T., Sharp, K., Motyer, A., Vukcevic, D., Delaneau, O., O'Connell, J., Cortes, A., Welsh, S., Young, A., Effingham, M., McVean, G., Leslie, S., Allen, N., Donnelly, P., & Marchini, J. (2018). The UK Biobank resource with deep phenotyping and genomic data. Nature, 562(7726), 203-209. https://doi.org/10.1038/s41586-018-0579-z
Cai, G., Shi, G., & Huang, Z. (2018). Gender specific effect of CETP rs708272 polymorphism on lipid and atherogenic index of plasma levels but not on the risk of coronary artery disease: A case-control study. Medicine, 97(49), e13514. https://doi.org/10.1097/MD.0000000000013514
Cannon, C. P., Shah, S., Dansky, H. M., Davidson, M., Brinton, E. A., Gotto, A. M., Stepanavage, M., Liu, S. X., Gibbons, P., Ashraf, T. B., Zafarino, J., Mitchel, Y., & Barter, P., Determining the Efficacy and Tolerability Investigators. (2010). Safety of anacetrapib in patients with or at high risk for coronary heart disease. New England Journal of Medicine, 363(25), 2406-2415. https://doi.org/10.1056/NEJMoa1009744
Catalano, G., Duchene, E., Julia, Z., Le Goff, W., Bruckert, E., Chapman, M. J., & Guerin, M. (2008). Cellular SR-BI and ABCA1-mediated cholesterol efflux are gender-specific in healthy subjects. Journal of Lipid Research, 49(3), 635-643. https://doi.org/10.1194/jlr.M700510-JLR200
Christen, T., Trompet, S., Noordam, R., Blauw, L. L., Gast, K. B., Rensen, P. C. N., Willems van Dijk, K., Rosendaal, F. R., de Mutsert, R., & Jukema, J. W., NEO study. (2018). Mendelian randomization analysis of cholesteryl ester transfer protein and subclinical atherosclerosis: A population-based study. Journal of Clinical Lipidology, 12(1), 137-144. https://doi.org/10.1016/j.jacl.2017.10.023
Cohen, J. C., Boerwinkle, E., Mosley, T. H., & Hobbs, H. H. (2006). Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. New England Journal of Medicine, 354(12), 1264-1272 http://www.nejm.org/doi/abs/10.1056/NEJMoa054013
Cole, C. B., Nikpay, M., Lau, P., Stewart, A. F. R., Davies, R. W., Wells, G. A., Dent, R., & McPherson, R. (2014). Adiposity significantly modifies genetic risk for dyslipidemia. Journal of Lipid Research, 55(11), 2416-2422. https://doi.org/10.1194/jlr.P052522
Coscia, C., Gill, D., Benítez, R., Pérez, T., Malats, N., & Burgess, S. (2022). Avoiding collider bias in Mendelian randomization when performing stratified analyses. European Journal of Epidemiology, 37(7), 671-682. https://doi.org/10.1007/s10654-022-00879-0
Dachet, C., Poirier, O., Cambien, F., Chapman, J., & Rouis, M. (2000). New functional promoter polymorphism, CETP/−629, in cholesteryl ester transfer protein (CETP) gene related to CETP mass and high density lipoprotein cholesterol levels: Role of Sp1/Sp3 in transcriptional regulation. Arteriosclerosis, Thrombosis, and Vascular Biology, 20(2), 507-515. https://doi.org/10.1161/01.atv.20.2.507
Davies, N. M., Holmes, M. V., & Davey Smith, G. (2018). Reading Mendelian randomisation studies: A guide, glossary, and checklist for clinicians. BMJ, 362, k601. https://doi.org/10.1136/bmj.k601
Dedoussis, G. V., Panagiotakos, D. B., Louizou, E., Mantoglou, I., Chrysohoou, C., Lamnisou, K., Pitsavos, C., & Stefanadis, C. (2007). Cholesteryl ester-transfer protein (CETP) polymorphism and the association of acute coronary syndromes by obesity status in Greek subjects: The CARDIO2000-GENE study. Human Heredity, 63(3-4), 155-161. https://doi.org/10.1159/000099827
Ference, B. A., Kastelein, J. J. P., Ginsberg, H. N., Chapman, M. J., Nicholls, S. J., Ray, K. K., Packard, C. J., Laufs, U., Brook, R. D., Oliver-Williams, C., Butterworth, A. S., Danesh, J., Smith, G. D., Catapano, A. L., & Sabatine, M. S. (2017). Association of genetic variants related to CETP inhibitors and statins with lipoprotein levels and cardiovascular risk. Journal of the American Medical Association, 318(10), 947-956. https://doi.org/10.1001/jama.2017.11467
Gamache, I., Legault, M.-A., Grenier, J.-C., Sanchez, R., Rhéaume, E., Asgari, S., Barhdadi, A., Zada, Y. F., Trochet, H., Luo, Y., Lecca, L., Murray, M., Raychaudhuri, S., Tardif, J.-C., Dubé, M.-P., & Hussin, J. (2021). A sex-specific evolutionary interaction between ADCY9 and CETP. eLife, 10, 10. https://doi.org/10.7554/eLife.69198
HPS3/TIMI55-REVEAL Collaborative Group, Bowman, L., Hopewell, J. C., Chen, F., Wallendszus, K., Stevens, W., Collins, R., Wiviott, S. D., Cannon, C. P., Braunwald, E., Sammons, E., & Landray, M. J. (2017). Effects of Anacetrapib in patients with atherosclerotic vascular disease. New England Journal of Medicine, 377(13), 1217-1227. https://doi.org/10.1056/NEJMoa1706444
Izem, L., Liu, Y., & Morton, R. E. (2020). Exon 9-deleted CETP inhibits full length-CETP synthesis and promotes cellular triglyceride storage. Journal of Lipid Research, 61(3), 422-431. https://doi.org/10.1194/jlr.RA120000583
Izem, L., & Morton, R. E. (2007). Possible role for intracellular cholesteryl ester transfer protein in adipocyte lipid metabolism and storage. Journal of Biological Chemistry, 282(30), 21856-21865. https://doi.org/10.1074/jbc.M701075200
Kark, J. D., Sinnreich, R., Leitersdorf, E., Friedlander, Y., Shpitzen, S., & Luc, G. (2000). Taq1B CETP polymorphism, plasma CETP, lipoproteins, apolipoproteins and sex differences in a Jewish population sample characterized by low HDL-cholesterol. Atherosclerosis, 151(2), 509-518. https://doi.org/10.1016/s0021-9150(99)00408-6
Kettunen, J., Demirkan, A., Würtz, P., Draisma, H. H. M., Haller, T., Rawal, R., Vaarhorst, A., Kangas, A. J., Lyytikäinen, L.-P., Pirinen, M., Pool, R., Sarin, A.-P., Soininen, P., Tukiainen, T., Wang, Q., Tiainen, M., Tynkkynen, T., Amin, N., Zeller, T., … Ala-Korpela, M. (2016). Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA. Nature Communications, 7, 11122. https://doi.org/10.1038/ncomms11122
Kettunen, J., Holmes, M. V., Allara, E., Anufrieva, O., Ohukainen, P., Oliver-Williams, C., Wang, Q., Tillin, T., Hughes, A. D., Kähönen, M., Lehtimäki, T., Viikari, J., Raitakari, O. T., Salomaa, V., Järvelin, M.-R., Perola, M., Davey Smith, G., Chaturvedi, N., Danesh, J., … Ala-Korpela, M. (2019). Lipoprotein signatures of cholesteryl ester transfer protein and HMG-CoA reductase inhibition. PLoS Biology, 17(12), e3000572. https://doi.org/10.1371/journal.pbio.3000572
Khera, A. V., Cuchel, M., de la Llera-Moya, M., Rodrigues, A., Burke, M. F., Jafri, K., French, B. C., Phillips, J. A., Mucksavage, M. L., Wilensky, R. L., Mohler, E. R., Rothblat, G. H., & Rader, D. J. (2011). Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. New England Journal of Medicine, 364(2), 127-135. https://doi.org/10.1056/NEJMoa1001689
King, E. A., Davis, J. W., & Degner, J. F. (2019). Are drug targets with genetic support twice as likely to be approved? Revised estimates of the impact of genetic support for drug mechanisms on the probability of drug approval. PLoS Genetics, 15(12), e1008489. https://doi.org/10.1371/journal.pgen.1008489
Klingel, S. L., Roke, K., Hidalgo, B., Aslibekyan, S., Straka, R. J., An, P., Province, M. A., Hopkins, P. N., Arnett, D. K., Ordovas, J. M., Lai, C.-Q., & Mutch, D. M. (2017). Sex differences in blood HDL-c, the total cholesterol/HDL-c ratio, and palmitoleic acid are not associated with variants in common candidate genes. Lipids, 52(12), 969-980. https://doi.org/10.1007/s11745-017-4307-5
Kronenberg, F., Mora, S., Stroes, E. S. G., Ference, B. A., Arsenault, B. J., Berglund, L., Dweck, M. R., Koschinsky, M., Lambert, G., Mach, F., McNeal, C. J., Moriarty, P. M., Natarajan, P., Nordestgaard, B. G., Parhofer, K. G., Virani, S. S., von Eckardstein, A., Watts, G. F., Stock, J. K., … Catapano, A. L. (2022). Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: A European Atherosclerosis Society consensus statement. European Heart Journal, 43, 3925-3946. https://doi.org/10.1093/eurheartj/ehac361
Lincoff, A. M., Nicholls, S. J., Riesmeyer, J. S., Barter, P. J., Brewer, H. B., Fox, K. A. A., Gibson, C. M., Granger, C., Menon, V., Montalescot, G., Rader, D., Tall, A. R., McErlean, E., Wolski, K., Ruotolo, G., Vangerow, B., Weerakkody, G., Goodman, S. G., Conde, D., … ACCELERATE Investigators. (2017). Evacetrapib and cardiovascular outcomes in high-risk vascular disease. New England Journal of Medicine, 376(20), 1933-1942. https://doi.org/10.1056/NEJMoa1609581
Low-Kam, C., Rhainds, D., Lo, K. S., Barhdadi, A., Boulé, M., Alem, S., Pedneault-Gagnon, V., Rhéaume, E., Dubé, M. P., Busseuil, D., Hegele, R. A., Lettre, G., & Tardif, J. C. (2018). Variants at the APOE/C1/C2/C4 locus modulate cholesterol efflux capacity independently of high-density lipoprotein cholesterol. Journal of the American Heart Association, 7(16), e009545. https://doi.org/10.1161/JAHA.118.009545
Melloni, C., Berger, J. S., Wang, T. Y., Gunes, F., Stebbins, A., Pieper, K. S., Dolor, R. J., Douglas, P. S., Mark, D. B., & Newby, L. K. (2010). Representation of women in randomized clinical trials of cardiovascular disease prevention. Circulation: Cardiovascular Quality and Outcomes, 3(2), 135-142. https://doi.org/10.1161/CIRCOUTCOMES.110.868307
Merriman, T. R. (2018). Application of genetic epidemiology to CETP (cholesteryl ester transfer protein) concentration and risk of cardiovascular disease. Circulation: Genomic and Precision Medicine, 11(5), 002138. https://doi.org/10.1161/CIRCGEN.118.002138
Metzinger, M. P., Saldanha, S., Gulati, J., Patel, K. V., El-Ghazali, A., Deodhar, S., Joshi, P. H., Ayers, C., & Rohatgi, A. (2020). Effect of anacetrapib on cholesterol efflux capacity: A substudy of the DEFINE trial. Journal of the American Heart Association, 9(24), e018136. https://doi.org/10.1161/JAHA.120.018136
Minikel, E. V., Karczewski, K. J., Martin, H. C., Cummings, B. B., Whiffin, N., Rhodes, D., Alföldi, J., Trembath, R. C., van Heel, D. A., Daly, M. J., Genome Aggregation Database Production Team, Genome Aggregation Database Consortium, Schreiber, S. L., MacArthur, D. G., Armean, I. M., Banks, E., Bergelson, L., Cibulskis, K., Collins, R. L., Connolly, K. M., Covarrubias, M., … Schunkert, H. (2020). Evaluating drug targets through human loss-of-function genetic variation. Nature, 581(7809), 459-464. https://doi.org/10.1038/s41586-020-2267-z
Nelson, M. R., Tipney, H., Painter, J. L., Shen, J., Nicoletti, P., Shen, Y., Floratos, A., Sham, P. C., Li, M. J., Wang, J., Cardon, L. R., Whittaker, J. C., & Sanseau, P. (2015). The support of human genetic evidence for approved drug indications. Nature Genetics, 47(8), 856-860. https://doi.org/10.1038/ng.3314
Nicholls, S. J., Ditmarsch, M., Kastelein, J. J., Rigby, S. P., Kling, D., Curcio, D. L., Alp, N. J., & Davidson, M. H. (2022). Lipid lowering effects of the CETP inhibitor obicetrapib in combination with high-intensity statins: A randomized phase 2 trial. Nature Medicine, 28(8), 1672-1678. https://doi.org/10.1038/s41591-022-01936-7
Niesor, E. J., Magg, C., Ogawa, N., Okamoto, H., von der Mark, E., Matile, H., Schmid, G., Clerc, R. G., Chaput, E., Blum-Kaelin, D., Huber, W., Thoma, R., Pflieger, P., Kakutani, M., Takahashi, D., Dernick, G., & Maugeais, C. (2010). Modulating cholesteryl ester transfer protein activity maintains efficient pre-β-HDL formation and increases reverse cholesterol transport. Journal of Lipid Research, 51(12), 3443-3454. https://doi.org/10.1194/jlr.M008706
Papp, A. C., Pinsonneault, J. K., Wang, D., Newman, L. C., Gong, Y., Johnson, J. A., Pepine, C. J., Kumari, M., Hingorani, A. D., Talmud, P. J., Shah, S., Humphries, S. E., & Sadee, W. (2012). Cholesteryl ester transfer protein (CETP) polymorphisms affect mRNA splicing, HDL levels, and sex-dependent cardiovascular risk. PLoS One, 7(3), e31930. https://doi.org/10.1371/journal.pone.0031930
Rothwell, P. M. (2006). Factors that can affect the external validity of randomised controlled trials. PLoS clinical trials, 1(1), e9. https://doi.org/10.1371/journal.pctr.0010009
Schaefer, E. J., Zech, L. A., Jenkins, L. L., Bronzert, T. J., Rubalcaba, E. A., Lindgren, F. T., Aamodt, R. L., Brewer, H. B., Jr. (1982). Human apolipoprotein A-I and A-II metabolism. Journal of Lipid Research, 23(6), 850-862. https://www.ncbi.nlm.nih.gov/pubmed/6813411
Schmidt, A. F., Finan, C., Gordillo-Marañón, M., Asselbergs, F. W., Freitag, D. F., Patel, R. S., Tyl, B., Chopade, S., Faraway, R., Zwierzyna, M., & Hingorani, A. D. (2020). Genetic drug target validation using Mendelian randomisation. Nature Communications, 11(1), 3255. https://doi.org/10.1038/s41467-020-16969-0
Schwartz, G. G., Olsson, A. G., Abt, M., Ballantyne, C. M., Barter, P. J., Brumm, J., Chaitman, B. R., Holme, I. M., Kallend, D., Leiter, L. A., Leitersdorf, E., McMurray, J. J. V., Mundl, H., Nicholls, S. J., Shah, P. K., Tardif, J.-C., & Wright, R. S., dal-OUTCOMES Investigators. (2012). Effects of dalcetrapib in patients with a recent acute coronary syndrome. New England Journal of Medicine, 367(22), 2089-2099. https://doi.org/10.1056/NEJMoa1206797
Sull, J. W., Kim, S., & Jee, S. H. (2019). Effects of obesity and family history of diabetes on the association of CETP rs6499861 with HDL-C level in Korean populations. Journal of Lipid and Atherosclerosis, 8(2), 252-257. https://doi.org/10.12997/jla.2019.8.2.252
Szustakowski, J. D., Balasubramanian, S., Kvikstad, E., Khalid, S., Bronson, P. G., Sasson, A., Wong, E., Liu, D., Wade Davis, J., Haefliger, C., Katrina Loomis, A., Mikkilineni, R., Noh, H. J., Wadhawan, S., Bai, X., Hawes, A., Krasheninina, O., Ulloa, R., Lopez, A. E., … UKB-ESC Research Team. (2021). Advancing human genetics research and drug discovery through exome sequencing of the UK Biobank. Nature Genetics, 53(7), 942-948. https://doi.org/10.1038/s41588-021-00885-0
Tardif, J.-C., Rhainds, D., Brodeur, M., Feroz Zada, Y., Fouodjio, R., Provost, S., Boulé, M., Alem, S., Grégoire, J. C., L'Allier, P. L., Ibrahim, R., Guertin, M.-C., Mongrain, I., Olsson, A. G., Schwartz, G. G., Rhéaume, E., & Dubé, M.-P. (2016). Genotype-dependent effects of dalcetrapib on cholesterol efflux and inflammation: Concordance with clinical outcomes. Circulation: Cardiovascular Genetics, 9(4), 340-348. https://doi.org/10.1161/CIRCGENETICS.116.001405
Thomas, T., Zhou, H., Karmally, W., Ramakrishnan, R., Holleran, S., Liu, Y., Jumes, P., Wagner, J. A., Hubbard, B., Previs, S. F., Roddy, T., Johnson-Levonas, A. O., Gutstein, D. E., Marcovina, S. M., Rader, D. J., Ginsberg, H. N., Millar, J. S., & Reyes-Soffer, G. (2017). CETP (cholesteryl ester transfer protein) inhibition with anacetrapib decreases production of lipoprotein(a) in mildly hypercholesterolemic subjects. Arteriosclerosis, Thrombosis, and Vascular Biology, 37(9), 1770-1775. https://doi.org/10.1161/ATVBAHA.117.309549
Thompson, J., Lloyd, D., Lira, M., & Milos, P. (2004). Cholesteryl ester transfer protein promoter single-nucleotide polymorphisms in Sp1-binding sites affect transcription and are associated with high-density lipoprotein cholesterol. Clinical Genetics, 66(3), 223-228. https://doi.org/10.1111/j.1399-0004.2004.00289.x
Villard, E. F., EI Khoury, P., Guerin, M., Bruckert, E., Clement, K., Bonnefont-Rousselot, D., Bittar, R., Le Goff, W., & Guerin, M. (2013). Genetic determination of plasma cholesterol efflux capacity is gender-specific and independent of HDL-cholesterol levels. Arteriosclerosis, Thrombosis, and Vascular Biology, 33(4), 822-828. https://doi.org/10.1161/ATVBAHA.112.300979
Wang, Y., van der Tuin, S., Tjeerdema, N., van Dam, A. D., Rensen, S. S., Hendrikx, T., Berbée, J. F. P., Atanasovska, B., Fu, J., Hoekstra, M., Bekkering, S., Riksen, N. P., Buurman, W. A., Greve, J. W., Hofker, M. H., Shiri-Sverdlov, R., Meijer, O. C., Smit, J. W. A., Havekes, L. M., … Rensen, P. C. N. (2015). Plasma cholesteryl ester transfer protein is predominantly derived from Kupffer cells. Hepatology, 62(6), 1710-1722. https://doi.org/10.1002/hep.27985
Yakerson, A. (2019). Women in clinical trials: A review of policy development and health equity in the Canadian context. International journal for equity in health, 18(1), 56. https://doi.org/10.1186/s12939-019-0954-x