Association of CETP Gene Polymorphisms and Haplotypes with Acute Heart Rate Response to Exercise.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Cholesterol Ester Transfer Proteins*/genetics ; Haplotypes* ; Polymorphism, Single Nucleotide* ; Heart Rate*/genetics ; Exercise*; Humans ; Male ; Female ; Middle Aged ; Adult ; Cholesterol, HDL/blood ; Aged ; Hungary

Polymorphisms in the cholesteryl ester transfer protein ( CETP ) gene are known to be strongly associated with increased cardiovascular risk, primarily through their effects on the lipid profile and consequently on atherosclerotic risk. The acute heart rate response (AHRR) to physical activity is closely related to individual cardiovascular health. This study aimed to investigate the effect of CETP gene polymorphisms on AHRR. Our analysis examines the association of five single nucleotide polymorphisms (SNPs; rs1532624, rs5882, rs708272, rs7499892, and rs9989419) and their haplotypes (H) in the CETP gene with AHRR in 607 people from the Hungarian population. Individual AHRR in the present study was assessed using the YMCA 3-min step test and was estimated as the difference between resting and post-exercise heart rate, i.e., delta heart rate (ΔHR). To exclude the direct confounding effect of the CETP gene on the lipid profile, adjustments for TG and HDL-C levels, next to conventional risk factors, were applied in the statistical analyses. Among the examined five SNPs, two showed a significant association with lower ΔHR (rs1532624-C dominant : B = -8.41, p < 0.001; rs708272-G dominant : B = -8.33, p < 0.001) and reduced the risk of adverse AHRR (rs1532624-C dominant : OR = 0.44, p = 0.004; rs708272-G dominant : OR = 0.43, p = 0.003). Among the ten haplotypes, two showed significant association with lower ΔHR (H3-CAGCA: B = -6.81, p = 0.003; H9-CGGCG: B = -14.64, p = 0.015) and lower risk of adverse AHRR (H3-CAGCA: OR = 0.58, p = 0.040; H9-CGGCG: OR = 0.05, p = 0.009) compared to the reference haplotype (H1-AGACG). Our study is the first to report a significant association between CETP gene polymorphisms and AHRR. It also confirms that the association of the CETP gene with cardiovascular risk is mediated by changes in heart rate in response to physical activity, in addition to its effect on lipid profile.

Antioxidants (Basel). 2022 Aug 31;11(9):. (PMID: 36139808)
Front Cardiovasc Med. 2023 Dec 07;10:1260679. (PMID: 38146445)
Vasc Health Risk Manag. 2021 Nov 13;17:701-711. (PMID: 34803382)
Mol Biol Rep. 2018 Dec;45(6):1929-1935. (PMID: 30178218)
J Hypertens. 2003 Mar;21(3):477-80. (PMID: 12640235)
Anim Genet. 2015 Dec;46(6):702-6. (PMID: 26477338)
Cell Mol Life Sci. 2019 Jun;76(12):2391-2409. (PMID: 30919020)
Atherosclerosis. 2017 Aug;263:119-126. (PMID: 28624686)
Biomolecules. 2019 Nov 14;9(11):. (PMID: 31739638)
Mayo Clin Proc. 2010 Jun;85(6):522-6. (PMID: 20511482)
Int J Cardiol. 2008 Jun 6;126(3):302-12. (PMID: 18068835)
Int J Mol Sci. 2023 Jun 17;24(12):. (PMID: 37373432)
Int J Exerc Sci. 2021 Dec 01;15(4):58-78. (PMID: 36895843)
Ann Neurol. 2016 Nov;80(5):730-740. (PMID: 27717122)
Int J Environ Res Public Health. 2020 Nov 05;17(21):. (PMID: 33167476)
Ann Clin Res. 1971 Dec;3(6):404-32. (PMID: 4945367)
Int J Environ Res Public Health. 2021 Sep 03;18(17):. (PMID: 34501887)
Cardiology. 2020;145(4):236-250. (PMID: 32172237)
Circ Genom Precis Med. 2018 May;11(5):e002034. (PMID: 29728394)
J Lipid Res. 2003 Jun;44(6):1080-93. (PMID: 12639975)
Pharmacol Res. 2023 Nov;197:106972. (PMID: 37898443)
Pharmacogenet Genomics. 2012 Feb;22(2):95-104. (PMID: 22143414)
Int J Environ Res Public Health. 2020 Jul 04;17(13):. (PMID: 32635565)
Atherosclerosis. 2014 Dec;237(2):777-83. (PMID: 25463120)
Int J Mol Sci. 2024 Mar 13;25(6):. (PMID: 38542212)
Adv Exp Med Biol. 2020;1276:15-25. (PMID: 32705591)
Clin Exp Hypertens. 2004 Oct-Nov;26(7-8):637-44. (PMID: 15702618)
JAMA Cardiol. 2022 Jan 1;7(1):55-64. (PMID: 34613338)
J Hypertens. 2011 May;29(5):863-8. (PMID: 21430561)
Genes (Basel). 2020 Jan 03;11(1):. (PMID: 31947886)
Ann Intern Med. 1993 Mar 15;118(6):436-47. (PMID: 8439119)
Curr Vasc Pharmacol. 2017;15(3):238-247. (PMID: 28137212)
PLoS One. 2015 Aug 27;10(8):e0136915. (PMID: 26313355)
Bioinformatics. 2006 Aug 1;22(15):1928-9. (PMID: 16720584)
Biol Res Nurs. 2020 Jul;22(3):421-422. (PMID: 32207318)
J Lipid Res. 1993 Aug;34(8):1255-74. (PMID: 8409761)
Biomolecules. 2021 Jan 07;11(1):. (PMID: 33430172)
Arch Med Sci. 2016 Dec 1;12(6):1188-1198. (PMID: 27904507)
Genes (Basel). 2020 Feb 26;11(3):. (PMID: 32110997)
J Lipid Res. 2004 Nov;45(11):1967-74. (PMID: 15342674)

GINOP-2.3.2-15-2016-00005 European Regional Development Fund; TK2016-78 Hungarian Academy of Sciences; TKCS-2021/32 Hungarian Research Network - HUN-REN; K_20, project No. 135784 National Research, Development, and Innovation Fund of Hungary; RRF-2.3.1-21-2022-00006 National Research, Development and Innovation Office; ÚNKP-23-5-DE-494 National Research, Development, and Innovation Fund of Hungary; BO/00513/23/5 Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences

Keywords: acute heart rate response; cardiovascular risk; cholesteryl ester transfer protein; genomics; haplotype; single nucleotide polymorphism

0 (Cholesterol Ester Transfer Proteins)
0 (CETP protein, human)
0 (Cholesterol, HDL)

Date Created: 20240829 Date Completed: 20240829 Latest Revision: 20240911

20240911

PMC11354538

10.3390/ijms25168587

39201274