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

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
• Single nucleotide polymorphism
• Intercellular adhesion molecule 1
• ICAM1 gene
• Resting heart rate