{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T14:24:19Z","timestamp":1780496659207,"version":"3.54.1"},"reference-count":42,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,3,6]],"date-time":"2020-03-06T00:00:00Z","timestamp":1583452800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Ministry of Health, Labour and Welfare in Japan"},{"name":"Actelion Pharmaceuticals Japan"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Rheum Dis"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Hypoxia\u2010inducible factor (HIF)1\u03b1 is induced by endothelial cells under hypoxic conditions, suggesting that HIF1\u03b1 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 <jats:italic>HIF1A<\/jats:italic> gene are associated with susceptibility to SSc and its complications, including pulmonary arterial hypertension (PAH).<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>This study involved 182 Japanese SSc patients (discovery cohort) and 178 healthy controls. Four SNPs (rs11549465, rs11549467, rs1957757, and rs12434438) of the <jats:italic>HIF1A<\/jats:italic> gene were genotyped using specific TaqMan probes. We also employed another SSc cohort (N\u00a0=\u00a0135) to validate the significant results of SNPs found in the discovery SSc cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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 (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.012). These results were validated using another SSc cohort (N\u00a0=\u00a0135, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.006). Moreover, the AA genotype was significantly associated with the severity of PAH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Although <jats:italic>HIF1A<\/jats:italic> 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.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1756-185x.13822","type":"journal-article","created":{"date-parts":[[2020,3,7]],"date-time":"2020-03-07T03:14:31Z","timestamp":1583550871000},"page":"674-680","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Single nucleotide polymorphisms of the <i>HIF1A<\/i> gene are associated with susceptibility to pulmonary arterial hypertension in systemic sclerosis and contribute to SSc\u2010PAH disease 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