Lack of association between the −839C/T polymorphism in the SLC6A3 gene promoter and schizophrenia in the Iranian population

Galehdari, Hamid; Shiva, Hosseini; Foroughmand, Ali Mohammad; Musaviun, Mohsen; Khatami, Saeed Reza; Pooryasin, Atefeh; Ajam, Tahereh; Haidari, Maryam

doi:10.1007/s12041-009-0046-6

Cited by 3 publications

(1 citation statement)

References 19 publications

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“…SNP rs2652511 (−841 bp) was associated with SCZ in Chinese, but not in Iranian samples. 69 They are approximately 8 kb downstream of rs1478435, but display high LD with each other (see SNPs # 7 and 8 vs #22 in supplementary figure 6), suggesting that the Chinese findings are likely to be LD-based signals. In another study, rs3756450 (−2600 bp) was found to be significantly associated with SCZ, 21 but that finding has not yet been replicated in other cohorts.…”

Section: Comparison With Previous Association Findingsmentioning

confidence: 99%

Increased NigralSLC6A3Activity in Schizophrenia Patients: Findings From the Toronto–McLean Cohorts

Kennedy

Xiong

et al. 2015

SCHBUL

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SLC6A3, which encodes the primary regulator of extracellular dopamine (DA) concentration, the DA transporter, has been implicated in schizophrenia (SCZ). However, the details of its genetic effect on risk remain largely unknown. The purpose of this candidate gene study was to identify a specificSLC6A3activity associated with SCZ by using functional genetic approaches. We first examined gene activity in DA neurons isolated from case-control postmortem nigral tissue and found that the averageSLC6A3mRNA level in controls was only 0.37-fold of that in cases (P= .0034). To understand this expression difference, we examined the association of 10 genetic markers, mostly located in the promoter region, with SCZ in 1717 subjects collected from Toronto and McLean cohorts, including 881 controls and 836 cases and identified the 5' promoter SNP rs1478435 as having a significant association signal (uncorrectedPvalue: .00462; adjustedPvalue: .0319) in unrelated Caucasians. Allele T was over-represented in controls (OR = .75); T-carrier controls had decreased mRNA levels in nigral DA neurons, contributing to the reduced activity in the controls. In vitro functional analysis confirmed that T carriers displayed attenuated enhancement of promoter activity. These findings collectively suggest that increased nigralSLC6A3activity may be a risk factor for SCZ, and may help to explain high rates of comorbidity with substance abuse.

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Section: Comparison With Previous Association Findingsmentioning

confidence: 99%