Serotonin transporter gene polymorphisms: ethnic difference and possible association with bipolar affective disorder

Abstract

There is some evidence suggesting that a polymorphism of variable number of tandem repeats (VNTR) in the second intron of the serotonin transporter (5-HTT) gene and another variation which lies 1.2 kb upstream of the promoter of the gene (5-HTTLPR) are associated with affective disorders. However, conflicting results have also been reported. We examined an allelic association of these two polymorphisms in a Japanese sample of 191 patients with affective disorders (142 bipolar and 49 unipolar) and 212 controls. Substantial differences in the number and frequency of alleles between Caucasians and Japanese were observed for both polymorphisms. A significant association between the VNTR polymorphism and bipolar disorder (genotypic association: odds ratio 2.2, 95% CI 1.2-4.0; allelic association: odds ratio 1.7, 95% CI 1.0-3.0) was found, but not between the 5-HTTLPR polymorphism and bipolar disorder. No significant association with unipolar depression was detected using either genetic marker, although this may be attributable to the relatively small number of subjects with unipolar depression. Our results suggest that the VNTR itself or another unknown functional polymorphism which would be in linkage disequilibrium to the VNTR has an effect on susceptibility to bipolar disorder.

A Large Case–Control Study of Common Functional SLC6A4 and BDNF Variants in Obsessive–Compulsive Disorder

“…Although it has greater statistical power than family studies, its results can be spurious for loci that differ in their allelic frequencies between ethnicities. The 5-HTTLPR polymorphism is known to vary strongly between ethnicities (Gelernter et al, 1999;Greenberg et al, 2000;Kunugi et al, 1997), and we addressed this issue by only analyzing ethnically matched probands and three control groups. Our three control groups were derived from three different geographical locations, and we thus cannot completely rule out some degree of remaining hidden population stratification (despite lack of differences in allelic and genotypic frequencies among these samples), given the recent report by Hu et al (2006) that showed marked differences in allelic frequencies at the 5-HTTLPR locus between Caucasian populations, even though these were partially comprised of individuals with psychiatric diagnoses.…”

Population-based and family-based studies on the serotonin transporter gene polymorphisms and bipolar disorder: a systematic review and meta-analysis

“…48,59 The 31 papers finally selected reported 43 studies related to the review objective in total since each paper frequently reported several separate studies. In total, 17 population-based studies 9,14,33,34,38,46,50,51,56,60,61,66,[68][69][70] and six family-based studies 12,32,42,53,63,74 were about 5-HTTLPR. A total of 16 population-based studies 27,33,35,38,41,47,[49][50][51]54,56,58,60,61,70,75 and four family-based studies 12,52,57,63 were about the intron 2 VNTR.…”

“…According to the forest plot of the 5-HTTLPR, Mynett-Johnson et al (2000), 12 Hauser et al (2003) 34 and Rotondo et al (2002) 9 stood apart as an apparent cluster. The forest plot of the intron 2 VNTR showed Kunugi et al, 38 Heiden et al (2000) 35 and Collier et al (1996b) 58 as an apparent cluster. However, we could not identify any particular characteristics shared by these studies that might cause them to stand apart.…”

Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with selective serotonin reuptake inhibitor efficacy in depressed patients

“…Ethnicity and length of assessment might have also played a role in determining the heterogeneity among studies. Different allele frequencies between Caucasians and Asians, the s allele being present in 42% of Caucasians, but in 79% of Asians, 45 are a strong cause of heterogeneity. In fact, when Caucasians were analyzed separately, the heterogeneity disappeared but it still remained when Asians were analyzed Figure 4 Outcome data for l/l versus l/s and s/s in remission rate, response rate and response rate within 4 weeks in Caucasian subjects.…”