P2RX7: A bipolar and unipolar disorder candidate susceptibility gene?
The chromosomal region 12q24 has been previously implicated by linkage studies of both bipolar disorder and unipolar mood disorder and we have reported two pedigrees segregating both bipolar disorder and Darier's disease that show linkage across this region. The gene P2RX7 is located in this chromosomal region and has been recently reported as a susceptibility gene for bipolar disorder and unipolar depression. The non-synonymous SNP rs2230912 (resulting in amino-acid polymorphism Q460R) showed the strongest association and has been postulated to be pathogenically relevant. We have investigated this gene in a large UK case-control sample (bipolar I disorder N = 687, unipolar recurrent major depression N = 1,036, controls N = 1,204). Neither rs2230912 nor any of 8 other SNPs genotyped across P2RX7 was found to be associated with mood disorder in general, nor specifically with bipolar or unipolar disorder. Further, sequencing of our two chromosome 12-linked bipolar-Darier families showed no evidence of rare variants at P2RX7 that could explain the linkage. Our data do not provide support for rs2230912 or the other polymorphisms studied within the P2RX7 locus, being involved in susceptibility to mood disorders.
Green
Elaine K
EK
Department of Psychological Medicine, Wales College of Medicine, Cardiff University, Heath Park, UK. greenek@cf.ac.uk
Grozeva
Detelina
D
Raybould
Rachel
R
Elvidge
Gareth
G
Macgregor
Stuart
S
Craig
Ian
I
Farmer
Anne
A
McGuffin
Peter
P
Forty
Liz
L
Jones
Lisa
L
Jones
Ian
I
O'Donovan
Mick C
MC
Owen
Mike J
MJ
Kirov
George
G
Craddock
Nick
N
D019943:Amino Acid Substitution; D001714:Bipolar Disorder / Q000235:genetics; D016022:Case-Control Studies; D002881:Chromosomes, Human, Pair 12; D003866:Depressive Disorder / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D018048:Receptors, Purinergic P2 / Q000235:genetics*; D058486:Receptors, Purinergic P2X7; D006113:United Kingdom
C546468:P2RX7 protein, human; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7