title: Association study of the 2-bp deletion polymorphism in exon 6 of the CHRFAM7A gene with idiopathic generalized epilepsy.
abstract: There is evidence of linkage between the 15q13-q14 locus, containing the gene encoding the α7 subunit (CHRNA7) of the neuronal nicotinic acetylcholine receptor (nAChR) and its partially duplicated isoform (CHRFAM7A), and epilepsy. Additionally, a 2-bp deletion polymorphism (c.497-498delTG; rs67158670) in CHRFAM7A, resulting in a frame shift and truncation of the protein product, is associated with some neurological diseases. This study was designed to explore the possibility of an association of the c.497-498delTG polymorphism of CHRFAM7A with idiopathic generalized epilepsies (IGEs) in Polish children and young patients. The study included 197 IGE patients and 258 unrelated healthy individuals. The frequency of the CHRFAM7A c.497-498delTG polymorphism was determined in each group using heteroduplex analysis. An association between the c.497-498delTG polymorphism of CHRFAM7A and IGE was evidenced. It was demonstrated that the frequency of the CHRFAM7A 2-bp deletion carriers was significantly lower in the IGE patients than in the control group. The observed frequency of 2-bp deletion carriers was high in IGE subjects (64%), but significantly higher in control subjects (76%). Carriers of at least one copy of the -2 bp allele had halved their risk of IGE susceptibility (delTG/delTG and delTG/wild-type versus wild-type/wild-type: odds ratio=0.55; 95% confidence intervals=0.365-0.827; p=0.004). Moreover, it has been demonstrated that this polymorphic variant is associated with the c.524-12_524-11insGTT variation (rs10649395) in intron 7 of CHRFAM7A. Our study substantiates the involvement of the α7 subunit of nAChR in the pathophysiology of IGEs and indicates that the CHRFAM7A c.497-498TG deletion or a nearby polymorphism may play a role in the pathogenesis of IGE. Further work should concentrate on ascertaining the exact mechanism of this polymorphism's effect and its relationship with IGE.
authors.affiliation: 1 Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences , Poznan, Poland .
authors.forename: Agata
authors.initials: A
authors.lastname: Rozycka
authors.forename: Jolanta
authors.initials: J
authors.lastname: Dorszewska
authors.forename: Barbara
authors.initials: B
authors.lastname: Steinborn
authors.forename: Margarita
authors.initials: M
authors.lastname: Lianeri
authors.forename: Anna
authors.initials: A
authors.lastname: Winczewska-Wiktor
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Sniezawska
authors.forename: Kamila
authors.initials: K
authors.lastname: Wisniewska
authors.forename: Pawel P
authors.initials: PP
authors.lastname: Jagodzinski
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D016001:Confidence Intervals; D004829:Epilepsy, Generalized / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D020180:Heteroduplex Analysis; D006801:Humans; D007438:Introns; D008297:Male; D011044:Poland; D011110:Polymorphism, Genetic; D017384:Sequence Deletion; D044465:White People / Q000235:genetics; D055815:Young Adult; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000235:genetics*
chemical_list: C579167:Chrna7 protein, human; D064569:alpha7 Nicotinic Acetylcholine Receptor
references.citation: Eur J Hum Genet. 2013 Jan;21(1):76-81
references.pmid: 22588665
references.citation: Epilepsy Res. 2002 Apr;49(2):157-72
references.pmid: 12049804
references.citation: J Affect Disord. 2001 Sep;66(1):79-82
references.pmid: 11532536
references.citation: Am J Med Genet. 2001 Jan 8;105(1):20-2
references.pmid: 11424985
references.citation: Epilepsia. 2003 Aug;44(8):1113-7
references.pmid: 12887446
references.citation: Neurosci Lett. 2004 Jan 23;355(1-2):69-72
references.pmid: 14729237
references.citation: Nat Genet. 2008 Mar;40(3):322-8
references.pmid: 18278044
references.citation: Epilepsia. 2011 Dec;52(12):e194-8
references.pmid: 22050399
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2003 Nov 15;123B(1):39-49
references.pmid: 14582144
references.citation: Hum Mol Genet. 2000 Jun 12;9(10):1465-72
references.pmid: 10888596
references.citation: Biochem Pharmacol. 2011 Oct 15;82(8):904-14
references.pmid: 21718690
references.citation: Genomics. 1998 Sep 1;52(2):173-85
references.pmid: 9782083
references.citation: Pediatr Neurol. 2007 Sep;37(3):157-64
references.pmid: 17765802
references.citation: Eur J Med Genet. 2011 Jul-Aug;54(4):e441-5
references.pmid: 21596161
references.citation: Genes Brain Behav. 2008 Feb;7(1):37-45
references.pmid: 17504249
references.citation: Hum Mol Genet. 1997 Aug;6(8):1329-34
references.pmid: 9259280
references.citation: Nat Genet. 2009 Feb;41(2):160-2
references.pmid: 19136953
references.citation: Epilepsia. 2001;42 Suppl 3:31-5
references.pmid: 11520320
references.citation: Epilepsia. 2005;46 Suppl 9:10-4
references.pmid: 16302871
references.citation: J Comp Neurol. 1997 Oct 27;387(3):385-98
references.pmid: 9335422
references.citation: Neurology. 1998 Dec;51(6):1608-12
references.pmid: 9855510
references.citation: Seizure. 2009 Oct;18(8):601-3
references.pmid: 19577488
references.citation: Epilepsia. 2005;46 Suppl 9:21-33
references.pmid: 16302873
references.citation: J Neurosci. 1999 Sep 15;19(18):7711-20
references.pmid: 10479675
references.citation: J Biol Chem. 2011 Jan 7;286(1):594-606
references.pmid: 21047781
references.citation: FEBS Lett. 2009 May 19;583(10):1599-604
references.pmid: 19383498
references.citation: Hum Mol Genet. 2009 Oct 1;18(19):3626-31
references.pmid: 19592580
references.citation: Am J Med Genet. 2000 Apr 3;96(2):196-201
references.pmid: 10893497
references.citation: Eur J Hum Genet. 2008 Nov;16(11):1364-71
references.pmid: 18545269
references.citation: Am J Hum Genet. 2001 Jan;68(1):225-31
references.pmid: 11104662
references.citation: Epilepsia. 1989 Jul-Aug;30(4):389-99
references.pmid: 2502382
references.citation: Epilepsia. 2011 Oct;52(10):e139-42
references.pmid: 21777232
references.citation: Hum Mutat. 2010 Jul;31(7):840-50
references.pmid: 20506139
references.citation: Brain Res. 2009 Sep 29;1291:1-11
references.pmid: 19631623
references.citation: Brain. 2010 Jan;133(Pt 1):23-32
references.pmid: 19843651
references.citation: Mol Psychiatry. 2002;7(9):1006-11
references.pmid: 12399955
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2006 Sep 5;141B(6):571-5
references.pmid: 16823804
references.citation: Genomics. 2002 Feb;79(2):197-209
references.pmid: 11829490
references.citation: Am J Psychiatry. 2006 Oct;163(10):1832-4
references.pmid: 17012698
references.citation: Eur J Hum Genet. 2009 Feb;17(2):149-50
references.pmid: 18854863
references.citation: PLoS Genet. 2010 May 20;6(5):e1000962
references.pmid: 20502679