Association of multiple DRD2 polymorphisms with anorexia nervosa.
To investigate whether the dopaminergic system plays a role in the etiology of anorexia nervosa (AN) via the dopamine D2 receptor, we investigated association and transmission disequilibrium at seven single-nucleotide polymorphisms (SNPs) spanning about 75 kbp of the gene DRD2. We studied 191 probands with a DSM-IV diagnosis of AN, 457 parents and affected relatives with a DSM-IV eating disorder diagnosis, and 98 unrelated, female, normal weight controls. The -141 C/- insertion/deletion (-141 Indel), previously shown to affect DRD2 transcription efficiency, and multiple exon seven polymorphisms, one of which has previously been shown to affect DRD2 transcript stability, exhibited statistically significant association with diagnosis in haplotype transmission disequilibrium and in haplotype case : control analyses. Significant linkage disequilibrium between the -141 Indel and two exon seven SNPs (939Y and 957Y) was observed over a distance of >50 kbp in the AN probands but not in the controls. Genetically transmitted variation in D2 dopamine receptor expression mediated by functional polymorphisms affecting transcription and translation efficiency may play a role in vulnerability to AN.
Bergen
Andrew W
AW
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7236, USA. bergena@mail.nih.gov
Yeager
Meredith
M
Welch
Robert A
RA
Haque
Kashif
K
Ganjei
J Kelly
JK
van den Bree
Marianne B M
MB
Mazzanti
Chiara
C
Nardi
Irma
I
Fichter
Manfred M
MM
Halmi
Katherine A
KA
Kaplan
Allan S
AS
Strober
Michael
M
Treasure
Janet
J
Woodside
D Blake
DB
Bulik
Cynthia M
CM
Bacanu
Silviu-Alin
SA
Devlin
Bernie
B
Berrettini
Wade H
WH
Goldman
David
D
Kaye
Walter H
WH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000856:Anorexia Nervosa / Q000235:genetics*; D016009:Chi-Square Distribution; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*
D017448:Receptors, Dopamine D2