Polymorphisms and haplotype of ROCK2 associate with high altitude essential hypertension in native high altitude Ladakhi Indian population: a preliminary study

Abstract

Background and objectives: High-altitude essential hypertension (HAEH) is a disease occurring in permanent residents of high-altitude regions. The disease is characterized with SBP ≥140 mmHg and DBP ≥90 mmHg. HAEH is known to run in families, i.e. the disease has genetic component. Rho-associated coiled-coil containing protein kinase 2 (ROCK2) is a stress-activated serine-threonine kinase known to disturb vascular-homeostasis leading to an increase in systemic vascular resistance, hallmark of HAEH. ROCK2 is implicated in sea-level essential hypertension but its role in HAEH is yet to be elucidated. Methods: The present study deals with genotyping 13 polymorphisms of ROCK2 gene in demographicaly matched human cases (n = 65) and controls (n = 38) by Sequenom MS (TOF)-based MassARRAY platform using iPLEX Gold technology. Results: A significant association was observed for GG genotype (SNP, rs978906), AA genotype (SNP, rs6753921), GG genotype (SNP, rs10495582) and AA genotype (SNP, rs2230774) with HAEH (p < 0.05). The 4 SNPs were tagged to each other and formed a 35 kb LD block (r²> 0.90). Haplotype AGCC, composed of wild-type alleles of the SNPs was over represented in controls. In contrast, haplotype GAGA, composed of variant-alleles was observed to be in higher proportion in cases. Moreover, SBP levels (mmHg) were higher in cases with risk genotype against the ones having protective genotype (p = 0.05). Bioinformatic analysis revealed binding of a critical transcription factor, SRF to variant-allele G of SNP rs10495582. SRF has been reported in previous studies to promote ROCK2 transcriptional expression. Interpretation and conclusions: The data clearly suggests association of ROCK2 polymorphisms and haplotypes with HAEH.

• HAEH
• haplotype
• ROCK2
• SNPs

Acknowledgements

We thank the Director, CSIR-Institute of Genomics and Integrative Biology, Delhi for providing necessary facilities and constant encouragement; Medical staff at SNM Hospital, Leh, Ladakh, Jammu and Kashmir, for providing precious study samples; and volunteers for participating in the study.

Declaration of interest

The authors have declared that there are no conflicts of interest.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Funding

The authors thank the Council of Scientific and Industrial Research (CSIR; www.csir.res.in/) for financially supporting under the projects [SIP0006]. University Grants Commission (UGC; http://www.ugc.ac.in/) for fellowship was provided to PP.