title: Serotonin-related FEV gene variant in the sudden infant death syndrome is a common polymorphism in the African-American population.
abstract: An important subset of the sudden infant death syndrome (SIDS) is associated with multiple serotonergic (5-HT) abnormalities in regions of the medulla oblongata. The mouse ortholog of the fifth Ewing variant gene (FEV) is critical for 5-HT neuronal development. A putatively rare intronic variant [IVS2-191_190insA, here referred to as c.128-(191_192)dupA] has been reported as a SIDS-associated mutation in an African-American population. We tested this association in an independent dataset: 137 autopsied cases (78 SIDS, 59 controls) and an additional 296 control DNA samples from Coriell Cell Repositories. In addition to the c.128-(191_192)dupA variant, we observed an associated single-base deletion [c.128-(301-306)delG] in a subset of the samples. Neither of the two FEV variants showed significant association with SIDS in either the African-American subgroup or the overall cohort. Although we found a significant association of c.128-(191_192)dupA with SIDS when San Diego Hispanic SIDS cases were compared with San Diego Hispanic controls plus Mexican controls (p = 0.04), this became nonsignificant after multiple testing correction. Among Coriell controls, 33 of 99 (33%) African-American and 0 of 197 (0%) of the remaining controls carry the polymorphism (c.128-(191_192)dupA). The polymorphism seems to be a common, likely nonpathogenic, variant in the African-American population.
authors.affiliation: Department of Pathology, Enders Building Room 1111, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA. kevin.broadbelt@childrens.harvard.edu
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Broadbelt
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Barger
authors.forename: David S
authors.initials: DS
authors.lastname: Paterson
authors.forename: Ingrid A
authors.initials: IA
authors.lastname: Holm
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Haas
authors.forename: Henry F
authors.initials: HF
authors.lastname: Krous
authors.forename: Hannah C
authors.initials: HC
authors.lastname: Kinney
authors.forename: Kyriacos
authors.initials: K
authors.lastname: Markianos
authors.forename: Alan H
authors.initials: AH
authors.lastname: Beggs
mesh_terms: D001741:Black or African American / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics*; D007223:Infant; D007438:Introns / Q000235:genetics; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012701:Serotonin / Q000378:metabolism; D013398:Sudden Infant Death / Q000235:genetics*; D014157:Transcription Factors
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; C474280:FEV protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors; D012701:Serotonin
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