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In a study of 29 unrelated patients with Postural Orthostatic Tachycardia Syndrome, candidate genes including SLC6A2 were screened for coding variants (PMID:15946904). Systematic sequencing of SLC6A2 revealed no Ala457Pro or other rare coding mutations in NET, and identified common polymorphisms at amino acids 16 (Arg16Gly) and 27 (Gln27Glu) with allele frequencies comparable to those in Caucasian controls (PMID:15946904). No variant demonstrated familial segregation or enrichment in affected individuals, and functional data did not support a monogenic mechanism. Consequently, there is no evidence of a causal role for SLC6A2 in POTS pathogenesis. These findings dispute a primary association and do not support clinical genetic testing of SLC6A2 for POTS.
Gene–Disease AssociationDisputed29 unrelated probands screened; no causative SLC6A2 variants identified; allele frequencies mirror controls ([PMID:15946904]) Genetic EvidenceLimitedNo rare or segregating SLC6A2 variants in 29 POTS patients; common polymorphisms not enriched ([PMID:15946904]) Functional EvidenceLimitedNo functional studies linking SLC6A2 variants to POTS; associations are physiological rather than monogenic |