title: Investigation of the association between Rho/Rho-kinase gene polymorphisms and systemic sclerosis.
abstract: Systemic sclerosis (SSc) is a disease characterized by inflammation, vascular abnormalities and fibrosis. The role of Rho/Rho-kinase pathway was demonstrated in the pathogenesis of fibrosis, inflammation and vascular abnormalities. This study was aimed to investigate the relation between SSc and Rho/Rho-kinase gene polymorphisms. The study included 339 patients with SSc and 302 healthy subjects who were apparently healthy and at similar age and gender. Genotype distributions and allele frequencies were detected by using Chi-square test or Fisher's exact Chi-square test between groups, and the haplotype analysis was applied using online program (SHEsis). Significant association was found in a polymorphism in the ROCK1 gene (rs35996865), a polymorphism in ROCK2 gene (rs10178332), a polymorphism in RhoA gene (rs2177268) and two polymorphisms in RhoC gene (rs11102522 and rs11538960) with SSc disease (p < 0.0022). In this study, association between SSc disease and Rho/Rho-kinase gene polymorphisms was investigated for the first time; significant associations between ROCK1, ROCK2, RhoA and RhoC gene polymorphisms and SSc disease were demonstrated. The results strongly suggest that this SNP may be an important risk factor for development of SSc. However, further validation of these findings in an independent cohort is necessary.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, School of Medicine, Uludag University, Görükle Kampusu, 16059, Nilüfer, Bursa, Turkey. drpehlivan@hotmail.com.
authors.forename: Yavuz
authors.initials: Y
authors.lastname: Pehlivan
authors.affiliation: Department of Rheumatology, Fırat University Faculty of Medicine, Elazig, Turkey.
authors.forename: Servet
authors.initials: S
authors.lastname: Yolbas
authors.affiliation: Department of Rheumatology, Kahramanmaras Sutcu Imam University Faculty of Medicine, Kahramanmaras, Turkey.
authors.forename: Gozde Yıldırım
authors.initials: GY
authors.lastname: Cetin
authors.affiliation: Department of Rheumatology, Marmara University Faculty of Medicine, Istanbul, Turkey.
authors.forename: Fatma
authors.initials: F
authors.lastname: Alibaz-Oner
authors.affiliation: Department of Rheumatology, Istanbul Bilim University Faculty of Medicine, Istanbul, Turkey.
authors.forename: Yonca
authors.initials: Y
authors.lastname: Cagatay
authors.affiliation: Department of Rheumatology, Istanbul Bilim University Faculty of Medicine, Istanbul, Turkey.
authors.forename: Neslihan
authors.initials: N
authors.lastname: Yilmaz
authors.affiliation: Department of Medical Biology, Gaziantep University Faculty of Medicine, Gaziantep, Turkey.
authors.forename: Serdar
authors.initials: S
authors.lastname: Oztuzcu
authors.affiliation: Department of Rheumatology, Trakya University Faculty of Medicine, Edirne, Turkey.
authors.forename: Salim
authors.initials: S
authors.lastname: Donmez
authors.affiliation: Department of Rheumatology, Ondokuz Mayıs University Faculty of Medicine, Samsun, Turkey.
authors.forename: Metin
authors.initials: M
authors.lastname: Ozgen
authors.affiliation: Department of Rheumatology, Fırat University Faculty of Medicine, Elazig, Turkey.
authors.forename: Suleyman Serdar
authors.initials: SS
authors.lastname: Koca
authors.affiliation: Department of Rheumatology, Trakya University Faculty of Medicine, Edirne, Turkey.
authors.forename: Omer Nuri
authors.initials: ON
authors.lastname: Pamuk
authors.affiliation: Department of Rheumatology, Ondokuz Mayıs University Faculty of Medicine, Samsun, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Sayarlıoglu
authors.affiliation: Department of Rheumatology, Gaziantep University Faculty of Medicine, Gaziantep, Turkey.
authors.forename: Bunyamin
authors.initials: B
authors.lastname: Kisacik
authors.affiliation: Department of Rheumatology, Marmara University Faculty of Medicine, Istanbul, Turkey.
authors.forename: Haner
authors.initials: H
authors.lastname: Direskeneli
authors.affiliation: Department of Medical Pharmacology, Gaziantep University Faculty of Medicine, Gaziantep, Turkey.
authors.forename: Abdullah Tuncay
authors.initials: AT
authors.lastname: Demiryurek
authors.affiliation: Department of Rheumatology, Gaziantep University Faculty of Medicine, Gaziantep, Turkey.
authors.forename: Ahmet Mesut
authors.initials: AM
authors.lastname: Onat
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012595:Scleroderma, Systemic / Q000175:diagnosis / Q000235:genetics*; D014421:Turkey; D020741:rho GTP-Binding Proteins / Q000235:genetics*; D054460:rho-Associated Kinases / Q000235:genetics*; D020742:rhoA GTP-Binding Protein / Q000235:genetics*; D000075024:rhoC GTP-Binding Protein
chemical_list: C066737:RHOA protein, human; C515851:ROCK1 protein, human; C515852:ROCK2 protein, human; D054460:rho-Associated Kinases; C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D000075024:rhoC GTP-Binding Protein
keywords: Early diagnosis; Pathogenesis; Rho/Rho-kinase; Systemic sclerosis