Association Study Between the Triallelic Polymorphism of SLC6A4 Gene and Eating Disorders
American Journal of Psychiatry and Neuroscience
Volume 6, Issue 4, December 2018, Pages: 104-107
Received: Oct. 2, 2018;
Accepted: Oct. 24, 2018;
Published: Dec. 21, 2018
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Beatriz Camarena, Department of Pharmacogenetics, National Institute of Psychiatry Ramon de la Fuente Muñiz, Mexico City, Mexico
Sandra Hernandez, Department of Pharmacogenetics, National Institute of Psychiatry Ramon de la Fuente Muñiz, Mexico City, Mexico
Laura Gonzalez, Eating Disorders Clinic, National Institute of Psychiatry Ramon de la Fuente Muñiz, Mexico City, Mexico
Griselda Flores, Hospital and Continuous Psychiatric Care, National Institute of Psychiatry Ramon de la Fuente Muñiz, Mexico City, Mexico
David Luna, Eating Disorders Clinic, National Institute of Psychiatry Ramon de la Fuente Muñiz, Mexico City, Mexico
Alejandro Aguilar, Department of Pharmacogenetics, National Institute of Psychiatry Ramon de la Fuente Muñiz, Mexico City, Mexico
Alejandro Caballero, Eating Disorders Clinic, National Institute of Psychiatry Ramon de la Fuente Muñiz, Mexico City, Mexico
The serotonin transporter is encoded by the SLC6A4 gene and has been an interesting candidate for anorexia nervosa (AN) and bulimia nervosa (BN). The present study analyzed the association between the triallelic model of the SLC6A4 gene and eating disorders in Mexican population. Materials and Methods: The 5-HTTLPR/rs25531 polymorphism was analyzed in 458 eating disorder patients and 337 control subjects. Genotype and allele analyses were examined in 206 BN and 79 AN patients and compared with the control group. Furthermore, genotype and allele analyses were performed on AN-Spectrum (AN-R, AN-BP and AN-EDNOS) and BN-Spectrum (BN-P, BN-NP and BN-EDNOS) groups and compared with the control group. Results: Case-control analysis showed that BN patients had an increased frequency of the S/LG alleles compared to controls (c2=6.9, df=1, p=0.0088). However, no association was found between AN and the 5-HTTLPR/rs25531 polymorphism (c2=3.3, df=1, p=0.0654). Also, an association was observed in genotype distribution when comparing AN-spectrum and control groups (c2=10.1, df=2, p=0.0069); however, analysis of allele frequencies did not show differences after Bonferroni correction (c2=5.6, df=1, p=0.0177). Finally, analysis of BN-Spectrum showed a high frequency of S/LG alleles compared to control group (c2=7.3, df=1, p=0.007). Conclusion: The low activity alleles of the 5- HTTLPR/rs25531 polymorphism of the SLC6A4 gene may play a significant role in the etiology of BN subtypes in Mexican population.
Association Study Between the Triallelic Polymorphism of SLC6A4 Gene and Eating Disorders, American Journal of Psychiatry and Neuroscience.
Vol. 6, No. 4,
2018, pp. 104-107.
Heils A, Teufel A, Petri S, Stöber G, Riederer P, Bengel D, et al. Allelic variation of human serotonin transporter gene expression. J Neurochem. 1996;66(6):2621-24.
Hu XZ, Lipsky RH, Zhu G, Akhtar LA, Taubman J, Greenberg BD, et al. Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder. Am J Hum Genet. 2006;78(5):815-26.
Lee Y, Lin PY. Association between serotonin transporter gene polymorphism and eating disorders: a meta-analytic study. Int J Eat Disord. 2010;43(6):498-504.
Calati R, De Ronchi D, Bellini M, Serretti A. The 5-HTTLPR polymorphism and eating disorders: a meta-analysis. Int J Eat Disord. 2011;44(3):191-9.
Chen W, Qian J, Pu D, Ge H, Wu J. The Association of 5-HTTLPR Gene Polymorphisms and Eating Disorder: A Meta-Analysis. 2015; J Psychol Psychother 5:214.
Solmi M, Gallicchio D, Collantoni E, Correll CU, Clementi M, Pinato C, et al. Serotonin transporter gene polymorphism in eating disorders: Data from a new biobank and META-analysis of previous studies. World J Biol Psychiatry. 2016 Jun;17(4):244-57.
Polsinelli GN, Levitan RN, De Luca V: 5-HTTLPR polymorphism in bulimia nervosa: a multiple-model meta-analysis. Psychiat Genet. 2012;22(5):219-25.
Murphy DL, Maile MS, Vogt NM: 5HTTLPR: White Knight or Dark Blight? ACS Chem Neurosci. 2013;4(1):13-5.
First MB, Spitzer RL, Gibbon M, Williams JBW: Structures clinical interview for DSM-IV axis I disorders-patient edition (SCID-I/P version 2.0). New York: Biometrics Research Department 1995, New York State Psychiatric Institute.
Gauderman WJ, Morrison JM: QUANTO 1.1: A computer program for power and sample size calculations for genetic-epidemiology studies, 2006. http://hydra.usc.edu/gxe.
Murdoch JD, Speed WC, Pakstis AJ, Heffelfinger CE, Kidd KK. Worldwide population variation and haplotype analysis at the serotonin transporter gene SLC6A4 and implications for association studies. Biol Psychiatry. 2013;74(12):879-89.
Camarena B, Rinetti G, Cruz C, Hernández S, de la Fuente JR, Nicolini H. Association study of the serotonin transporter gene polymorphism in obsessive-compulsive disorder. Int J Neuropsychopharmacol. 2001;4(3):269-72.
Di Bella DD, Catalano M, Cavallini MC, Riboldi C, Bellodi L. Serotonin transporter linked polymorphic region in anorexia nervosa and bulimia nervosa. Mol Psychiatry. 2000;5(3):233-4.
Matsushita S, Suzuki K, Murayama M, Nishiguchi N, Hishimoto A, Takeda A, et al. Serotonin transporter regulatory region polymorphism is associated with anorexia nervosa. Am J Med Genet B Neuropsychiatr Genet. 2004;128B(1):114-7.
Chen J, Kang Q, Jiang W, Fan J, Zhang M, Yu S, Zhang C. The 5-HTTLPR confers susceptibility to anorexia nervosa in Han Chinese: evidence from a case-control and family-based study. PLoS One. 2015 Mar 18;10(3).
Kiezebrink K, Mann ET, Bujac SR, Stubbins MJ, Campbell DA, Blundell JE. Evidence of complex involvement of serotonergic genes with restrictive and binge purge subtypes of anorexia nervosa. World J Biol Psychiatry. 2010;11(6):824-33.
Rybakowski F, Slopien A, Dmitrzak-Weglarz M, Czerski P, Rajewski A, Hauser, J. The 5-HT2A -1438 A/G and 5-HTTLPR polymorphisms and personality dimensions in adolescent anorexia nervosa: association study. Neuropsychobiology. 2006;53(1):33-9.
Sundaramurthy D, Pieri LF, Gape H, Markham AF, Campbell DA. Analysis of the serotonin transporter gene linked polymorphism (5-HTTLPR) in anorexia nervosa. Am J Med Genet. 2000;96(1):53-5.
Monteleone P, Santonastaso P, Mauri M, Bellodi L, Erzegovesi S, Fuschino A, et al. Investigation of the serotonin transporter regulatory region polymorphism in bulimia nervosa: relationships to harm avoidance, nutritional parameters, and psychiatric comorbidity. Psychosom Med. 2006;68(1):99-103.
Steiger H, Richardson J, Schmitz N, Joober R, Israel M, Bruce K. R, et al. Association of trait-defined, eating-disorder sub-phenotypes with (biallelic and triallelic) 5HTTLPR variations. J Psychiatry Res. 2009;43(13):1086-1094.
Mata J, Gotlib IH. 5-HTTLPR moderates the relation between changes in depressive and bulimic symptoms in adolescent girls: a longitudinal study. Int J Eat Disord. 2011;44(5):383-8.
Richardson J, Steiger H, Schmitz N, Joober R, Bruce KR, Israel M, et al. Relevance of the 5-HTTLPR polymorphism and childhood abuse to increased psychiatric comorbidity in women with bulimia-spectrum disorders. J Clin Psychiatry. 2008;69(6):981-90.
Steiger H, Richardson J, Joober R, Gauvin L, Israel M, Bruce KR, et al. The 5HTTLPR polymorphism, prior maltreatment and dramatic-erratic personality manifestations in women with bulimic syndromes. J Psychiatry Neurosci. 2007;32(5):354-62.
Castellini G, Ricca V, Lelli L, Bagnoli S, Lucenteforte E, Faravelli C, et al. Association between serotonin transporter gene polymorphism and eating disorders outcome: a 6-year follow-up study. Am J Med Genet B Neuropsychiatr Genet. 2012 Jul;159B(5):491-500.
Steiger H, Joober R, Israël M, Young SN, Ng Ying Kin NM, Gauvin L, et al. The 5HTTLPR polymorphism, psychopathologic symptoms, and platelet [3H-] paroxetine binding in bulimic syndromes. Int. J. Eat. Disord. 2005;37(1):57-60.
Camarena B, González L, Hernández S, Caballero A. 2012. SLC6A4 rare variant associated with eating disorders in Mexican patients. J Psychiatr Res. 2012;46(8): 1106-07.