title: CYBA (p22phox) variants associate with blood pressure and oxidative stress markers in hypertension: a replication study in populations of diverse altitudes.
abstract: CYBA (p22(phox)) is an integral constituent of the NADPH oxidases and is consequently a main component of oxidative stress, which is strongly associated with hypertension. This study investigates the contribution of CYBA polymorphisms toward the complex etiology of hypertension in two ethnically different populations, one located at a high altitude and the other at a low altitude. The significance of CYBA single nucleotide polymorphisms and their correlation with clinical and biochemical phenotypes were investigated in age- and ethnicity-matched unrelated permanent high-altitude residents (>3500 m) comprising 245 controls and 241 patients. The results were replicated in a second population comprising 935 controls and 545 patients who lived at a low altitude (<200 m). The analysis of covariance revealed that CYBA risk alleles and their haplotypes, rs8854A/rs9932581G/rs4873C and rs8854G/rs9932581G/rs4873C, were positively correlated with clinical parameters, for example, systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP), and biochemical parameters, for example, 8-isoPGF2α level, and inversely correlated with catalase activity in patients compared with controls (P⩽0.01, each). Conversely, the protective alleles and their haplotype, rs8854G/rs9932581A/rs4873T, were inversely correlated with SBP, DBP, MAP and 8-isoPGF2α level, and positively correlated with catalase activity (P⩽0.001, each). Furthermore, correlation analysis between the clinical and biochemical parameters revealed a positive correlation of SBP, DBP and MAP with 8-isoPGF2α levels and a negative correlation with catalase activity in both populations (P<0.0001, each). CYBA (p22(phox)) variants influence the markers of oxidative stress and are associated with hypertension.
authors: Functional Genomics Unit, CSIR-Institute of Genomics and Integrative Biology, Delhi, India.
authors: Rahul
authors: R
authors: Kumar
authors: 1] Functional Genomics Unit, CSIR-Institute of Genomics and Integrative Biology, Delhi, India [2] Academy of Scientific and Innovative Research, New Delhi, India.
authors: Samantha
authors: S
authors: Kohli
authors: Functional Genomics Unit, CSIR-Institute of Genomics and Integrative Biology, Delhi, India.
authors: Zahara
authors: Z
authors: Ali
authors: Functional Genomics Unit, CSIR-Institute of Genomics and Integrative Biology, Delhi, India.
authors: Kanika
authors: K
authors: Duhan
authors: Functional Genomics Unit, CSIR-Institute of Genomics and Integrative Biology, Delhi, India.
authors: Rekhbala
authors: R
authors: Ram
authors: Department of Cardiology, G.B. Pant hospital, New Delhi, India.
authors: Mohit
authors: M
authors: Gupta
authors: Department of Cardiology, G.B. Pant hospital, New Delhi, India.
authors: Sanjay
authors: S
authors: Tyagi
authors: Department of Medicine, S.N.M. hospital, Leh, Ladakh, India.
authors: Ghulam
authors: G
authors: Mohammad
authors: 1] Functional Genomics Unit, CSIR-Institute of Genomics and Integrative Biology, Delhi, India [2] Academy of Scientific and Innovative Research, New Delhi, India.
authors: Ma Qadar
authors: MQ
authors: Pasha
mesh_terms: D000328:Adult; D000483:Alleles; D000531:Altitude; D015415:Biomarkers; D001794:Blood Pressure / Q000235:genetics*; D002374:Catalase / Q000097:blood / Q000235:genetics; D003710:Demography; D005260:Female; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology*; D007194:India / Q000453:epidemiology; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D019255:NADPH Oxidases / Q000235:genetics*; D018384:Oxidative Stress / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D002374:Catalase; D019255:NADPH Oxidases; C086986:CYBA protein, human