Haplotype association study between DRD1 gene and bipolar type I affective disorder in two samples from Canada and Sardinia.
Based on the dopaminergic hypothesis, the dopamine D(1) receptor gene (DRD1) is considered to be a good candidate gene involved in the susceptibility of bipolar disorder (BP). Genetic association between three DRD1 single nucleotide polymorphisms (SNPs) (-800T/C, -48A/G, and 1403T/C) and bipolar type I (BP I) disorder was performed in a case-control sample of Sardinian origin (170 BP I and 209 controls) and in an enlarged sample (229 families) of BP I trios from Toronto. The haplotype analyses generated significant global chi-square in both samples (P-value 0.024 in Toronto and 0.00042 in Sardinian). The main representative haplotypes in both samples were the -800T/-48A/1403C and the -800C/-48G/1403T. Considering each group individually, the -800C/-48G/1403T was transmitted more frequently from parents to BP I probands in Toronto sample (nominally P-value = 0.047) and was more frequent in cases than in control subjects in Sardinian sample although showing no significant evidence of association (nominally P-value = 0.16) When the estimated haplotype counts of both samples were combined, the global chi(2) was significant (P-value = 0.00085) and the nominal P-value for the haplotype -800C/-48G/1403T was 0.01. The fact that the same haplotype shows a similar trend for association in samples originating from different ethnic backgrounds seems to imply that the -800C/-48G/1403T haplotype may be considered as a risk factor for BP I disorder.
Del Zompo
Maria
M
Department of Neurosciences B.B. Brodie, Section of Clinical Pharmacology, Center of Clinical Psychopharmacology, University of Cagliari, Cagliari, Italy. delzompo@unica.it
De Luca
Vincenzo
V
Severino
Giovanni
G
Ni
Xingqun
X
Mulas
Stefania
S
Congiu
Donatella
D
Piccardi
Maria Paola
MP
Kennedy
James L
JL
D000328:Adult; D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics*; D002170:Canada; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007558:Italy; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017447:Receptors, Dopamine D1 / Q000235:genetics*; D012307:Risk Factors
D017447:Receptors, Dopamine D1