Linkage disequilibrium of serotonin transporter gene and mood disorders

Background: Epidemiological studies have shown obvious familial aggregation of mood disorders. In serotonin system, serotonin transporter gene (5-HTT) is expressed mostly in the presynaptic membrane in the central nervous system, and plays an important role in serotonin reuptake into the presynaptic neurons. Therefore, some genes in relation to serotonin function are considered candidate genes for mood disorder susceptibility. Objective: To examine the molecular genetic association between mood disorder and serotonin transporter gene. Design: Group design method was used to observe the core families comprising the patients and their parents, with the parents serving as the internal control for analysis of linkage disequilibrium analysis by transmission/transmission disequilibrium test (TDT). Setting: Center of Mental Health of Shantou University, College of Basic Medical Science, Sun Yat-sen University, and Second Hospital Affiliated to Jining Medical College. Participants: Mood disorder core families were recruited from the inpatients and outpatients of Second Hospital Affiliated to Jining Medical College and Center of Mental Health of Shantou University between June 2001 and June 2002. All of the subjects involved were Chinese of Han Nationality. The diagnosis was made in accordance to the diagnostic criteria described for mood disorders of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Methods: Family survey was conducted using self-designed questionnaire, and all subjects underwent evaluation with Hamilton's Depression and Anxiety Scale and Bech-Rafaelsen Mania Scale. The genome DNA was obtained from all subjects for detecting of 5-HTT gene polymorphism in the promoter region (5-HTTLPR), the second intron (VNTR) and 3′ non-coding region (3′ UTRG/T) using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, and TDT was also conducted. Main outcome measures: Molecular genetic as sociation of the 3 alleles and their combinations in haploids with mood disorder. Results: Altogether 247 patients from 72 families were recruited, but only 232 patients from 72 core families were eligibal for heredity analysis. Two haploids with the combination of VNTR in 5-HTT gene and either of the 2 loci of 3′UTRG/T were found to associate with mood disorder (χ2= 4.08 by TDT, empirical P value=0.04 after 1 000 corrections by Monte Carlo simulation method), but no linkage disequilibrium was observed between 5-HTTLPR, VNTR, or 3′ UTRG/T allele in the other loci and mood disorder, nor was the linkage found in the haploids with combination of other loci. Conclusion: 5-HTT gene mig ht play a role in the genetic disposition of mood disorder.