No Association Study of SLC6A4 Polymorphisms with Korean Autism Spectrum Disorder

다국어 초록 (Multilingual Abstract)

Objectives : The serotonin transporter gene(SLC6A4) is one of the most widely studied candidate genes in autism spectrum disorder(ASD), but there have been conflicting results from studies into the association between SLC6A4 and ASD. The aim of this study was to evaluate the association between single nucleotide polymorphisms(SNPs) in the SLC6A4 gene and ASD in the Korean population. Methods : We selected 12 SNPs in SLC6A4 and observed the genotype of 151 Korean ASD trios. We tested the family-based association for each individual polymorphism and haplotype by using the standard TDT method in Haploview(http://www.broad.mit.edu/mpg/haploview/). Results : Through transmission-disequilibrium testing and haplotype analysis, we could not find any statistically significant transmitted allele or haplotype. In addition, a case-control association test with Korean HapMap data did not reveal any statistical significance. Conclusion : Although serotonin-related genes must be considered candidate genes for ASD, we suggest that common SNPs of SLC6A4 are not important markers for associations with Korean ASD.

참고문헌 (Reference)

1 Coutinho AM, "Variants of the serotonin transporter gene (SLC6A4) significantly contribute to hyperserotonemia in autism" 9 : 264-271, 2004

2 Kim SJ, "Transmission disequilibrium mapping at the serotonin transporter gene (SLC6A4) region in autistic disorder" 7 : 278-288, 2002

3 Cook EH, "The serotonin system in autism" 8 : 348-354, 1996

4 Persico AM, "Serotonin transporter gene promoter variants do not explain the hyperserotoninemia in autistic children" 7 : 795-800, 2002

5 Betancur C, "Serotonin transporter gene polymorphisms and hyperserotoninemia in autistic disorder" 7 : 67-71, 2002

6 Conroy J, "Serotonin transporter gene and autism: a haplotype analysis in an Irish autistic population" 9 : 587-593, 2004

7 Lange C, "Power and design considerations for a general class of family-based association tests: quantitative traits" 71 : 1330-1341, 2002

8 Veenstra-VanderWeele J, "Pharmacogenetics and the serotonin system: initial studies and future directions" 410 : 165-181, 2000

9 Cross S, "Molecular genetics of the platelet serotonin system in first-degree relatives of patients with autism" 33 : 353-360, 2008

10 Jones MB, "Modifier effects in autism at the MAO-A and DBH loci" 126 : 58-65, 2004

11 McCauley JL, "Linkage and association analysis at the serotonin transporter (SLC6A4) locus in a rigid-compulsive subset of autism" 127 : 104-112, 2004

12 Ramoz N, "Lack of evidence for association of the serotonin transporter gene SLC6A4 with autism" 60 : 186-191, 2006

13 Wu S, "Lack of evidence for association between the serotonin transporter gene (SLC6A4) polymorphisms and autism in the Chinese trios" 381 : 1-5, 2005

14 Persico AM, "Lack of association between serotonin transporter gene promoter variants and autistic disorder in two ethnically distinct samples" 96 : 123-127, 2000

15 Yoo HJ, "Korean version of Autism Diagnostic Observation Schedule (ADOS)" Hakji-sa 2007

16 Yoo HJ, "Korean version of Autism Diagnostic Interview - Revised (ADI-R)" Hakji-sa 2007

17 Anderson GM, "Genetics of childhood disorders: XLV. Autism, part 4: serotonin in autism" 4 : 1513-1516, 2002

18 Cho IH, "Family-based association study of 5-HTTLPR and the 5-HT2A receptor gene polymorphisms with autism spectrum disorder in Korean trios" 1139 : 34-41, 2007

19 Yirmiya N, "Evidence for an association with the serotonin transporter promoter region polymorphism and autism" 105 : 381-386, 2001

20 Abramson RK, "Elevated blood serotonin in autistic probands and their first-degree relatives" 19 : 397-407, 1989

21 Anderson GM, "Cohen DJ, Volkmar FR, Hoder EL, McPhedran P, et al. Whole blood serotonin in autistic and normal subjects" 28 : 885-900, 1987

22 Bailey A, "Autism as a strongly genetic disorder: evidence from a British twin study" 25 : 63-77, 1995

23 Lesch KP, "Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region" 274 : 1527-1531, 1996

24 Yoo HJ, "Association between PTGS2 polymorphism and autism spectrum disorders in Korean trios" 62 : 66-69, 2008

25 "A genomewide screen of 345 families for autism-susceptibility loci" 73 : 886-897, 2003

26 International Molecular Genetic Study of Autism Consortium, "A genomewide screen for autism: strong evidence for linkage to chromosomes 2q, 7q, and 16p" 69 : 570-581, 2001

27 McDougle CJ, "A double-blind, placebo-controlled study of fluvoxamine in adults with autistic disorder" 53 : 1001-1008, 1996

28 Gordon CT, "A double-blind comparison of clomipramine, desipramine, and placebo in the treatment of autistic disorder" 50 : 441-447, 1993

29 Zhong N, "5-HTTLPR variants not associated with autistic spectrum disorders" 2 : 129-131, 1999