title: Polymorphisms and haplotype of ROCK2 associate with high altitude essential hypertension in native high altitude Ladakhi Indian population: a preliminary study.
abstract: OBJECTIVE
  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 (r(2 )> 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.
  
  
  CONCLUSIONS
  The data clearly suggests association of ROCK2 polymorphisms and haplotypes with HAEH.
authors.affiliation: a CSIR-Institute of Genomics and Integrative Biology , Delhi , India .|b Department of Biotechnology , University of Pune , Ganeshkhind , Pune , Maharashtra , India , and.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Pandey
authors.affiliation: c Department of Medicine , SNM Hospital , Leh, Ladakh, Jammu and Kashmir , India.
authors.forename: Ghulam
authors.initials: G
authors.lastname: Mohammad
authors.affiliation: a CSIR-Institute of Genomics and Integrative Biology , Delhi , India .|b Department of Biotechnology , University of Pune , Ganeshkhind , Pune , Maharashtra , India , and.
authors.forename: Yogendra
authors.initials: Y
authors.lastname: Singh
authors.affiliation: a CSIR-Institute of Genomics and Integrative Biology , Delhi , India .|b Department of Biotechnology , University of Pune , Ganeshkhind , Pune , Maharashtra , India , and.
authors.forename: M A Qadar
authors.initials: MA
authors.lastname: Pasha
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000531:Altitude; D016022:Case-Control Studies; D000075222:Essential Hypertension; D005260:Female; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D007194:India; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D014655:Vascular Resistance / Q000235:genetics*; D044465:White People / Q000235:genetics*; D055815:Young Adult; D054460:rho-Associated Kinases / Q000235:genetics*
chemical_list: C515852:ROCK2 protein, human; D054460:rho-Associated Kinases
keywords: HAEH; ROCK2; SNPs; haplotype