한국인 자폐스펙트럼장애와 SLC6A4 유전다형성의 연관연구
No association study of SLC6A4 polymorphisms with Korean autism spectrum disorder
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Objective : 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.
Abstract
Objective : 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 (29)
- Bailey A, "Autism as a strongly genetic disorder: evidence from a British twin study", Psychol Med, 25, pp.63~77 (1995)
- Cross S, "Molecular genetics of the platelet serotonin system in first-degree relatives of patients with autism", Neuropsychopharmacology, 33, pp.353~360 (2008)
- Abramson RK, "Elevated blood serotonin in autistic probands and their first-degree relatives", J Autism Dev Disord, 19, pp.397~407 (1989)
- Anderson GM, "Cohen DJ, Volkmar FR, Hoder EL, McPhedran P, et al. Whole blood serotonin in autistic and normal subjects", J Child Psychol Psychiatry, 28, pp.885~900 (1987)
- Cook EH, "The serotonin system in autism", Curr Opin Pediatr, 8, pp.348~354 (1996)
- Anderson GM, "Genetics of childhood disorders: XLV. Autism, part 4: serotonin in autism", J Am Acad Child Adolesc Psychiatry, 4, pp.1513~1516 (2002)
- Gordon CT, "A double-blind comparison of clomipramine, desipramine, and placebo in the treatment of autistic disorder", Arch Gen Psychiatry, 50, pp.441~447 (1993)
- McDougle CJ, "A double-blind, placebo-controlled study of fluvoxamine in adults with autistic disorder", Arch Gen Psychiatry, 53, pp.1001~1008 (1996)
- Persico AM, "Serotonin transporter gene promoter variants do not explain the hyperserotoninemia in autistic children", Mol Psychiatry, 7, pp.795~800 (2002)
- Betancur C, "Serotonin transporter gene polymorphisms and hyperserotoninemia in autistic disorder", Mol Psychiatry, 7, pp.67~71 (2002)
- Jones MB, "Modifier effects in autism at the MAO-A and DBH loci", Am J Med Genet B Neuropsychiatr Genet, 126, pp.58~65 (2004)
- Veenstra-VanderWeele J, "Pharmacogenetics and the serotonin system: initial studies and future directions", Eur J Pharmacol, 410, pp.165~181 (2000)
- International Molecular Genetic Study of Autism Consortium, "A genomewide screen for autism: strong evidence for linkage to chromosomes 2q, 7q, and 16p", Am J Hum Genet, 69, pp.570~581 (2001)
- McCauley JL, "Linkage and association analysis at the serotonin transporter (SLC6A4) locus in a rigid-compulsive subset of autism", Am J Med Genet B Neuropsychiatr Genet, 127, pp.104~112 (2004)
- "A genomewide screen of 345 families for autism-susceptibility loci", Am J Hum Genet, 73, pp.886~897 (2003)
- Conroy J, "Serotonin transporter gene and autism: a haplotype analysis in an Irish autistic population", Mol Psychiatry, 9, pp.587~593 (2004)
- Kim SJ, "Transmission disequilibrium mapping at the serotonin transporter gene (SLC6A4) region in autistic disorder", Mol Psychiatry, 7, pp.278~288 (2002)
- Persico AM, "Lack of association between serotonin transporter gene promoter variants and autistic disorder in two ethnically distinct samples", Am J Med Genet, 96, pp.123~127 (2000)
- Yirmiya N, "Evidence for an association with the serotonin transporter promoter region polymorphism and autism", Am J Med Genet, 105, pp.381~386 (2001)
- Zhong N, "5-HTTLPR variants not associated with autistic spectrum disorders", Neurogenetics, 2, pp.129~131 (1999)
- Coutinho AM, "Variants of the serotonin transporter gene (SLC6A4) significantly contribute to hyperserotonemia in autism", Mol Psychiatry, 9, pp.264~271 (2004)
- Lesch KP, "Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region", Science, 274, pp.1527~1531 (1996)
- Wu S, "Lack of evidence for association between the serotonin transporter gene (SLC6A4) polymorphisms and autism in the Chinese trios", Neurosci Lett, 381, pp.1~5 (2005)
- Ramoz N, "Lack of evidence for association of the serotonin transporter gene SLC6A4 with autism", Biol Psychiatry, 60, pp.186~191 (2006)
- Cho IH, "Family-based association study of 5-HTTLPR and the 5-HT2A receptor gene polymorphisms with autism spectrum disorder in Korean trios", Brain Res, 1139, pp.34~41 (2007)
- Yoo HJ, "Association between PTGS2 polymorphism and autism spectrum disorders in Korean trios", Neurosci Res, 62, pp.66~69 (2008)
- Yoo HJ, "Korean version of Autism Diagnostic Interview - Revised (ADI-R)" (2007), Hakji-sa
- Yoo HJ, "Korean version of Autism Diagnostic Observation Schedule (ADOS)" (2007), Hakji-sa
- Lange C, "Power and design considerations for a general class of family-based association tests: quantitative traits", Am J Hum Genet, 71, pp.1330~1341 (2002)