ADRA1A gene is associated with BMI in chronic schizophrenia patients exposed to antipsychotics

Original Article - click here to go to article.

The Pharmacogenomics Journal advance online publication 17 November 2009; doi: 10.1038/tpj.2009.55

Y-R Liu^1,2,11, E-W Loh^1,11, T-H Lan^1,3,4, S-F Chen⁵, Y-H Yu⁶, Y-H Chang^1,7, C-J Huang⁸, T-M Hu⁹, K-M Lin¹, Y-T Yao² and H-J Chiu¹⁰

1. Division of Mental Health and Addiction Medicine, Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, Taiwan
2. Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan
3. Faculty of Medicine, National Yang Ming University, Taipei, Taiwan
4. Department of Psychiatry, Taichung Veterans General Hospital, Taichung, Taiwan
5. Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan
6. Department of Life Sciences and Institute of Genome Sciences, National Yang Ming University, Taipei, Taiwan
7. Institute of Public Health and Department of Public Health, National Yang Ming University, Taipei, Taiwan
8. Department of Industrial Engineering and Engineering Management, College of Engineering, National Tsing-Hua University, HsinChu, Taiwan
9. Department of Psychiatry, Yu-Li Veterans Hospital, Hualian County, Taiwan
10. Jianan Mental Hospital, Tainan County, Taiwan

Correspondence: Dr H-J Chiu, Department of Health, Jianan Mental Hospital, #80, Lane 870, Jhung-Shan Road, Rende Township, Tainan 717, Taiwan. E-mail: chiu8@mail2000.com.tw

¹¹These authors contributed equally to this study.

Received 28 April 2009; Revised 28 July 2009; Accepted 23 September 2009; Published online 17 November 2009.

Abstract

Noradrenaline and adrenaline are neurotransmitters of the sympathetic nervous system that interact with various adrenergic receptor (ADR) subtypes, and this regulates the basal metabolic rate, thermogenesis and efficiency of energy utilization. We examined a possible role of the gene coding for ADRA1A receptor in weight gain in schizophrenia subjects exposed to antipsychotics. A total of 401 schizophrenia in-patients treated with antipsychotics for >2 years were recruited and a final 394 DNA samples were genotyped. Their body mass indexes (BMIs) were recorded for 12 months and parameterized to be correlated in regression. Among the 58 single-nucleotide polymorphisms (SNPs) genotyped, 44 valid SNPs, which had minor allele frequency 0.03, were analyzed in statistics. Linear regression model with age, gender, diabetes, use of typical antipsychotics and use of atypical antipsychotics as covariates, with or without gender interaction, showed evidence of associations between the ADRA1A gene and BMI. Most of the SNPs associated with BMI are located in the promoter and intron regions, and being female appeared to enhance the gene effect. Our study suggests that the ADRA1A gene is involved in weight gain among schizophrenia patients treated with antipsychotics. Further molecular dissection of the ADRA1A gene warrants better understanding on weight gain mechanisms in schizophrenia.