Genetic Association Study of ADRB2-rs1042714 and the Elevation of Blood Pressure among the Hypertensive Malays from Peninsular Malaysia

Introduction: Hypertension (HT) is the risk factor associated with cardiovascular disease. Globally, prevalence of HT increases annually and it is estimated by year 2025, HT will affect 1.56 billion individuals (Kearney et al. 2005). The Malaysia National Health and Morbidity Survey 2019 (NHMS 2019) revealed that 30.0% of Malaysians have HT. However, only 45% of them had a blood pressure (BP) control after taking the anti-hypertensive medications (NHMS, 20119). HT is a multifactorial complex disorder involving a complex interplay between multiple genes and environmental factors involving high salt intake and obesity (Singh et al. 2017). Genetic factors suggested to contribute about 30-60% of BP variation (Ahn and Gupta 2018).
The sympathetic nervous system (SNS) is thought to partly play a role in the regulation of BP, via its mediation effect on vascular tone and cardiac contractility (Pojoga et al. 2006). ADRB2 is a candidate gene involved in this mechanism. However, its association with the susceptibility to HT and its impact on the elevation of BP remain inconclusive. Objective: Investigate the association of ADRB2 with the elevation of BP among Malays HT. Methods and materials: 1) 500 malays HT individuals recruited from PURE/REDISCOVER and UiTM primary care clinic. 418 Malays NT individuals recruited from PURE/REDISCOVER. 2) Genotyping 3) Genetic association study 4) Data Analysis: SPSS 5) Chi-square for association of genes and HT. Independent T-test for investigate the association of BP and HT. Results: Note: HT, elevated BP > 140/90 mmHg in SBP or DBP or in both SBP and DBP or on anti-HT medication. NT, normotension, BP <130/90 mmHg and not on anti-HT medication. Analysis of diplotype (GG/CC) frequency versus others showed no significant difference between HT and NT (p = 1.000). Same result observed in haplotype analysis (p = 0.908). Discussion/Conclusion: Both SNPs in ADRB2; rs1042713 and rs1042714 were reported to be associated with salt sensitivity (Liu et al. 2017). It was shown that individuals who carry the rs1042713- G allele had a higher risk of HT (Islam 2017) and rs1042714-G allele, caused the larger elevated in forearm blood flow and dilation of hand veins (Liu et al. 2010). However, no association observed between the both SNPs of ADRB2 gene and HT. Interestingly, the present study shows an association between ADRB2-rs1042714 and elevation of BP. The association is observed in female HT patients, therefore suggests a plausible role of sex hormone such as estrogen in the regulation of BP (Charkoudian. 2018). If proven to be true, this SNP could potentially be applied as a potential pharmacogenetic marker for HT treatment.