Serotonin-related FEV gene variant in the sudden infant death syndrome is a common polymorphism in the African-American population.
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.
Broadbelt
Kevin G
KG
Department of Pathology, Enders Building Room 1111, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA. kevin.broadbelt@childrens.harvard.edu
Barger
Melissa A
MA
Paterson
David S
DS
Holm
Ingrid A
IA
Haas
Elisabeth A
EA
Krous
Henry F
HF
Kinney
Hannah C
HC
Markianos
Kyriacos
K
Beggs
Alan H
AH
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
D017931:DNA Primers; D004268:DNA-Binding Proteins; C474280:FEV protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors; D012701:Serotonin
J Neurosci. 2005 Mar 9;25(10):2628-36
15758173
J Neuropathol Exp Neurol. 2005 Aug;64(8):689-94
16106217
Pediatr Res. 2007 Aug;62(2):180-2
17597646
BMJ. 1990 Jul 14;301(6743):85-9
2390588
Neuropediatrics. 2002 Jun;33(3):142-9
12200744
CMAJ. 2006 Jun 20;174(13):1861-9
16785462
Lancet. 2007 Nov 3;370(9598):1578-87
17980736
PLoS Genet. 2008 Dec;4(12):e1000294
19057673
J Neurosci. 2008 Nov 26;28(48):12748-58
19036967
Neurosci Lett. 2004 Mar 11;357(3):215-8
15003288
Hum Mutat. 2000;15(1):7-12
10612815
Biol Neonate. 1994;65(3-4):194-7
8038282
Auton Neurosci. 2007 Mar 30;132(1-2):81-102
17236817
Neuron. 2003 Jan 23;37(2):233-47
12546819
Rev Environ Health. 2006 Apr-Jun;21(2):81-103
16898673
Arch Dis Child. 1990 Apr;65(4):462-7
2189370
Dev Genes Evol. 2002 Feb;212(1):43-6
11875656
Am J Respir Crit Care Med. 2001 Aug 1;164(3):346-57
11500332
J Neuropathol Exp Neurol. 2000 May;59(5):377-84
10888367
N Engl J Med. 1992 Jun 4;326(23):1522-6
1579135
Pediatrics. 1994 May;93(5):814-9
8165085
Natl Vital Stat Rep. 2006 May 3;54(16):1-29
16711376
JAMA. 2006 Nov 1;296(17):2124-32
17077377
Am J Hum Genet. 2005 May;76(5):887-93
15789306
Pediatrics. 2004 Jul;114(1):234-8
15231934
Acta Neuropathol. 2009 Mar;117(3):257-65
19052756
J Neuropathol Exp Neurol. 2001 Mar;60(3):228-47
11245208
Development. 2004 Mar;131(5):1165-73
14973276
FEMS Immunol Med Microbiol. 2004 Sep 1;42(1):3-10
15325392
Proc Natl Acad Sci U S A. 2005 Nov 8;102(45):16472-7
16251278
J Neurosci. 2003 Nov 5;23(31):9961-7
14602809
JAMA. 2002 Dec 4;288(21):2717-23
12460095
Am J Epidemiol. 1996 Aug 1;144(3):300-5
8686699
Pediatr Pathol. 1991 Sep-Oct;11(5):677-84
1745639
Nat Neurosci. 2003 Sep;6(9):933-8
12897786
Forensic Sci Int. 2002 Sep 14;130 Suppl:S53-9
12350301