カワグチ　ヤスシ   KAWAGUCHI Yasushi   川口　鎮司    所属   医学部 医学科（東京女子医科大学病院）    職種   准教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	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.
掲載誌名	正式名：International journal of rheumatic diseases 略　 称：Int J Rheum Dis ISSNコード：1756185X/17561841
掲載区分	国外
巻・号・頁	23(5),pp.674-680
著者・共著者	TAKAGI KAE†, KAWAMOTO MANABU, HIGUCHI TOMOAKI, HARIGAI MASAYOSHI, KAWAGUCHI YASUSHI*
担当区分	責任著者
発行年月	2020/03/06
概要	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