The Epsin 4 gene on chromosome 5q, which encodes the clathrin-associated protein enthoprotin, is involved in the genetic susceptibility to schizophrenia.
Chromosome 5q33 is a region that has previously shown good evidence of linkage to schizophrenia, with four LOD scores >3.00 in independent linkage studies. We studied 450 unrelated white English, Irish, Welsh, and Scottish research subjects with schizophrenia and 450 ancestrally matched supernormal controls. Four adjacent markers at the 5' end of the Epsin 4 gene showed significant evidence of linkage disequilibrium with schizophrenia. These included two microsatellite markers, D5S1403 (P=.01) and AAAT11 (P=.009), and two single-nucleotide-polymorphism markers within the Epsin 4 gene, rs10046055 (P=.007) and rs254664 (P=.01). A series of different two- and three-marker haplotypes were also significantly associated with schizophrenia, as confirmed with a permutation test (HapA, P=.004; HapB, P=.0005; HapC, P=.007; and HapD, P=.01). The Epsin 4 gene encodes the clathrin-associated protein enthoprotin, which has a role in transport and stability of neurotransmitter vesicles at the synapses and within neurons. A genetically determined abnormality in the structure, function, or expression of enthoprotin is likely to be responsible for genetic susceptibility to a subtype of schizophrenia on chromosome 5q33.3.
Pimm
Jonathan
J
Molecular Psychiatry Laboratory, Department of Mental Health Sciences, University College London Medical School, Windeyer Institute of Medical Sciences, London, United Kingdom.
McQuillin
Andrew
A
Thirumalai
Srinivasa
S
Lawrence
Jacob
J
Quested
Digby
D
Bass
Nicholas
N
Lamb
Graham
G
Moorey
Helen
H
Datta
Susmita R
SR
Kalsi
Gursharan
G
Badacsonyi
Allison
A
Kelly
Katie
K
Morgan
Jenny
J
Punukollu
Bhaskar
B
Curtis
David
D
Gurling
Hugh
H
D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*
D033942:Adaptor Proteins, Vesicular Transport; C475910:CLINT1 protein, human; D002352:Carrier Proteins; C434483:EPN3 protein, human