Novel polymorphisms in the somatostatin receptor 5 (SSTR5) gene associated with bipolar affective disorder

The somatostatin receptor 5 (SSTR5) gene is a candidate gene for bipolar affective disorder (BPAD) as well as for other neuropsychiatric disorders. The gene is positioned on chromosome

16p13.3, a region that has been implicated by a few linkage studies to potentially harbor a disease susceptibility gene for BPAD. Recent evidence shows that the dopamine D2 receptor (DRD2)

and SSTR5 interact physically to form heterodimers with enhanced functional activity. Brain D2 dopamine receptors are one of the major targets of neuroleptic treatments in psychiatric

disorders. In this study we systematically screened the promoter and coding region of the SSTR5 gene for genetic variation that could contribute to the development of neuropsychiatric

disorders. Eleven novel single nucleotide polymorphisms (SNPs) were identified including four missense SNPs, Leu48Met, Ala52Val, Pro109Ser and Pro335Leu. We carried out an association study

of BPAD using 80 Danish cases and 144 control subjects, and replication analysis using 55 British cases and 88 control subjects. For the Danish population, association was suggested between

silent SNP G573A and BPAD (P = 0.008). For the British population we found association to BPAD with missense mutation Leu48Met (P = 0.003) and missense mutation Pro335Leu (P = 0.004). The

statistical significance of the association was, however, greatly reduced after correcting for multiple testing. When combining genotypes from Leu48Met and Pro335Leu into haplotypes,

association to BPAD was found in the British population (P = 0.0007). This haplotype association was not replicated in the Danish population. Our results may indicate that the SSTR5 gene is

involved in the etiology of BPAD or may exist in linkage disequilibrium with a susceptibility gene close to SSTR5. However, given the marginal statistical significance and the potential for

false-positive results in association studies with candidate genes, further studies are needed to clarify this hypothesis.

D16S85 was found on compound Z69706 and D16S521 was found on compound Z69719, both on contig NT_000655, at URL: http://www.ncbi.nlm.nih.gov/genome/guide/HsChr16.shtml.

Ewald H, Mors O, Flint T, Koed K, Eiberg H, Kruse TA . A possible locus for manic depressive illness on chromosome 16p13 Psychiatr Genet 1995; 5: 71–81

The SSTR5 clone used in this study was kindly provided by Dr Graeme I Bell, Howard Hughes Medical Institute. We thank Drs Robert Plomin (SGDP Centre) and Simon Lovestone (Old Age Psychiatry)

for access to the British control samples. This work was supported by the Danish Medical Research Council (9303757, 9602007, 9902685, 9902769), Fonden til Laegevidenskabens Fremme, Fonden

til Psykiatriens Fremme, The Psychiatric Research Foundation, The Eli and Egon Larsen Foundation, The Geert-Jørgensen Foundation, The Axel Thomsen Foundation, The Trier-Hansen Foundation,

and The Jacob Madsen Foundation.

Department of Clinical Biochemistry and Genetics, Odense University Hospital, Denmark

Mood Disorders Research Unit, Psychiatric Hospital in Aarhus, Denmark

Department of Psychological Medicine, Institute of Psychiatry, London, UK

Institute for Basic Psychiatric Research, Psychiatric Hospital in Aarhus, Denmark

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