樋口　智昭
   Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine
   Position   Endowed Assistant Professor
Article types Original article
Language English
Peer review Peer reviewed
Title Single nucleotide polymorphisms of the HIF1A gene are associated with susceptibility to pulmonary arterial hypertension in systemic sclerosis and contribute to SSc-PAH disease severity.
Journal Formal name：International journal of rheumatic diseases
Abbreviation：Int J Rheum Dis
ISSN code：1756185X/17561841
Domestic / ForeginForegin
Volume, Issue, Page 23(5),pp.674-680
Author and coauthor TAKAGI KAE†, KAWAMOTO MANABU, HIGUCHI TOMOAKI, HARIGAI MASAYOSHI, KAWAGUCHI YASUSHI*
Publication date 2020/03/06
Summary AIM:Hypoxia-inducible factor (HIF)1α is induced by endothelial cells under hypoxic conditions, suggesting that HIF1α may be involved in vascular impairment in patients with systemic sclerosis (SSc). The purpose of this study was to evaluate whether single nucleotide polymorphisms (SNPs) of the HIF1A gene are associated with susceptibility to SSc and its complications, including pulmonary arterial hypertension (PAH).METHOD:This study involved 182 Japanese SSc patients (discovery cohort) and 178 healthy controls. Four SNPs (rs11549465, rs11549467, rs1957757, and rs12434438) of the HIF1A gene were genotyped using specific TaqMan probes. We also employed another SSc cohort (N = 135) to validate the significant results of SNPs found in the discovery SSc cohort.RESULTS:The frequencies of the four SNPs did not show any significant differences between the SSc and healthy control groups. The AA genotype at rs12434438 was significantly higher in SSc patients with PAH than in those without PAH (P = .012). These results were validated using another SSc cohort (N = 135, P = .006). Moreover, the AA genotype was significantly associated with the severity of PAH.CONCLUSION:Although HIF1A gene polymorphisms were not associated with susceptibility to SSc, the AA genotype at rs12434438 was associated with a subset of SSc patients with severe PAH, suggesting that the rs12434438 SNP may contribute to the development of PAH with SSc.
DOI 10.1111/1756-185X.13822
PMID 32144871