Stewart S Evelyn, Fagerness Jesen A, Platko Jill, Smoller Jordan W, Scharf Jeremiah M, Illmann Cornelia, Jenike Eric, Chabane Nadia, Leboyer Marion, Delorme Richard, Jenike Michael A, Pauls David L
Psychiatric Neurodevelopmental and Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
Am J Med Genet B Neuropsychiatr Genet. 2007 Dec 5;144B(8):1027-33. doi: 10.1002/ajmg.b.30533.
Obsessive-Compulsive Disorder (OCD) is a debilitating illness with putative glutamatergic abnormalities. Two separate proximal haplotypes in the glutamate transporter gene, SLC1A1, were recently reported to be associated with OCD among males, but replication is required.
This study examines SLC1A1 as a candidate gene for OCD and explores gender influences. It was hypothesized that a significant association between SLC1A1 and OCD would be replicated in an independent sample of males but not females.
Family-based association candidate gene study.
Participants were recruited from tertiary care OCD specialty clinics.
OCD probands and their first degree relatives.
Association of OCD with genotypes of single nucleotide polymorphism (SNP) markers and related haplotypes.
Association between OCD and the three-marker haplotype rs12682807/ rs2072657/ rs301430, with overtransmission of A/T/T, was observed in both genders combined (global P = 0.0015) and in males (global P = 0.0031). Single-marker associations with OCD in the region (rs3780412 and rs2228622) demonstrated modest significance (permuted P = 0.045).
This study identifies a significant association between the SLC1A1 glutamate transporter gene and OCD in a haplotype overlapping with that recently reported.
强迫症（OCD）是一种伴有假定谷氨酸能异常的使人衰弱的疾病。最近有报道称，谷氨酸转运体基因SLC1A1中两个独立的近端单倍型与男性强迫症有关，但需要进行复制验证。
本研究将SLC1A1作为强迫症的候选基因进行检测，并探讨性别影响。研究假设SLC1A1与强迫症之间的显著关联将在男性独立样本中得到复制，而在女性中则不然。
基于家系的关联候选基因研究。
参与者从三级医疗强迫症专科诊所招募。
强迫症先证者及其一级亲属。
强迫症与单核苷酸多态性（SNP）标记基因型及相关单倍型的关联。
在合并的男女样本（总体P = 0.0015）和男性样本（总体P = 0.0031）中，均观察到强迫症与三联体单倍型rs12682807/ rs2072657/ rs301430（A/T/T过度传递）之间存在关联。该区域与强迫症的单标记关联（rs3780412和rs2228622）显示出适度的显著性（置换P = 0.045）。
本研究在一个与最近报道的单倍型重叠的区域，确定了SLC1A1谷氨酸转运体基因与强迫症之间存在显著关联。
