Associations between the rs5498 (A > G) and rs281432 (C > G) polymorphisms of the ICAM1 gene and atherosclerotic cardiovascular disease risk, including hypercholesterolemia

Naruemon Wechjakwen; Amornrat Aroonnual; Pattaneeya Prangthip; Ngamphol Soonthornworasiri; Pornpimol Panprathip Phienluphon; Jirayu Lainampetch; Karunee Kwanbunjan

doi:10.7717/peerj.12972

Associations between the rs5498 (A > G) and rs281432 (C > G) polymorphisms of the ICAM1 gene and atherosclerotic cardiovascular disease risk, including hypercholesterolemia

PeerJ. 2022 Mar 8:10:e12972. doi: 10.7717/peerj.12972. eCollection 2022.

Authors

Naruemon Wechjakwen¹, Amornrat Aroonnual¹, Pattaneeya Prangthip¹, Ngamphol Soonthornworasiri², Pornpimol Panprathip Phienluphon¹, Jirayu Lainampetch³, Karunee Kwanbunjan¹

Affiliations

¹ Department of Tropical Nutrition and Food Science, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
² Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
³ Department of Nutrition, Faculty of Public health, Mahidol University, Bangkok, Thailand.

Abstract

Background: Atherosclerotic cardiovascular disease (ASCVD) originates from complex risk factors, including age, gender, dyslipidemia, obesity, race, genetic and genetic variation. ICAM1 gene polymorphisms are a significant risk factor for ASCVD. However, the impact of the rs5498 and rs281432 polymorphisms on the prevalence of hypercholesterolemia (HCL) has not been reported. Therefore, we determine the relationships between single nucleotide polymorphisms (SNPs), including rs5498 and rs281432 on Intercellular adhesion molecule 1 gene (ICAM1) and ASCVD susceptibility in patients with HCL.

Methods: The clinical characteristics of 278 participants were assessed, and classified to groups having HCL and without HCL. ICAM1 SNPs genotyping was performed by DNA sequencing, and ICAM1 expression was measured using real-time PCR.

Results: Positive dominant model rs5498 participants had twice the risk of HCL (95% confidence interval (CI): [1.24-3.23], P = 0.005). The frequency of the G allele in rs5498 was 1.69 times higher in participants with HCL than in controls (95% CI [1.15-2.47], P = 0.007). Participants with the rs5498 AG or GG variants and high ICAM1 mRNA expression (≥3.12) had 2.49 times the risk (95% CI [1.42-4.38], P = 0.001), and those with a high LDL-C concentration (≥3.36 mmol/L) had 2.09 times the risk (95% CI [1.19-3.66], P = 0.010) of developing ASCVD compared with those with low ICAM1 mRNA and LDL-C levels. Interestingly, participants carrying the rs5498 AG or GG variants who had tachycardia (resting heart rates (RHRs) >100 beats/min) had a 5.02-times higher risk than those with a lower RHR (95% CI [1.35-18.63], P = 0.016).

Conclusions: It may consider the G allele in ICAM1 rs5498 is associated with a higher risk of ASCVD in Thai people with HCL, and is also positively associated with ICAM1 mRNA expression, LDL-C concentration, and RHR.

Keywords: Atherosclerotic cardiovascular disease; Hypercholesterolemia; ICAM1 gene; Intercellular adhesion molecule 1; Resting heart rate; Single nucleotide polymorphism.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Atherosclerosis* / epidemiology
Cardiovascular Diseases* / epidemiology
Cholesterol, LDL / genetics
Genetic Predisposition to Disease / genetics
Humans
Hypercholesterolemia* / epidemiology
Intercellular Adhesion Molecule-1 / genetics
Polymorphism, Single Nucleotide / genetics

Substances

Cholesterol, LDL
ICAM1 protein, human
Intercellular Adhesion Molecule-1

Grants and funding

The funding for this work was supported by the Faculty of Tropical Medicine and the Young Researcher Development Program 2019 of the National Research Council of Thailand (NRCT). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.