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• W2153410010 abstract "Serotonin is a key contributing factor in pulmonary arterial hypertension (PAH) by inducing pulmonary arterial smooth muscle cell (PA-SMC) proliferation. This relates specifically to the internalization process in PA-SMC of the serotonin transporter (SLC6A4 or 5-HTT). A long (L)/short (S) (44 base pair insertion) functional polymorphism within the promoter of the transporter SLC6A4 gene has been reported to be associated with familial and idiopathic PAH. Our objective was to determine whether polymorphisms of SLC6A4 confer susceptibility to SSc and its vascular phenotype.Three Tag single-nucleotide polymorphisms (SNP) (rs2066713, rs1042173, rs6354) chosen using Hapmap and linkage disequilibrium data were genotyped in a total cohort of 667 SSc patients (56 with PAH, 207 with digital ulcerations) and 447 controls. All individuals were of French Caucasian origin. L/S polymorphism genotyping was determined by polymerase chain reaction in a random subgroup of 364 SSc patients (34 with PAH, 138 with digital ulcerations) and 218 controls.Three polymorphisms (L/S, rs2066713, rs1042173) were in Hardy-Weinberg equilibrium in the control population, but rs6354 deviated. Allelic and genotypic frequencies for these 3 polymorphisms were similar in SSc patients and controls. Subphenotype analyses of subsets with PAH and digital ulceration did not detect any difference between SSc patients compared to controls.These results from a large cohort of European Caucasian SSc patients do not support the implication of SLC6A4 in the pathogenesis of SSc and its vascular subphenotypes. However, serotonin pathways remain good candidates to contribute to the vasculopathy of SSc." @default.
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• W2153410010 date "2010-04-15" @default.
• W2153410010 modified "2023-10-18" @default.
• W2153410010 title "Association Study of Serotonin Transporter Gene (SLC6A4) in Systemic Sclerosis in European Caucasian Populations" @default.
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• W2153410010 doi "https://doi.org/10.3899/jrheum.091156" @default.
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