Correlation between the-2548G/A Polymorphism of Leptin Gene and Antipsychotic-induced Weight Gain: A Meta-Analysis_Chinese Journal of Evidence-Based Medicine

Authors：

 LUOXue-mei ¹ ,  FANGYun ¹ , YANSi-min ²

1. Department of Medication, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China;
2. Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China;

Corresponding author：

FANGYun, Email: njglfy@163.com

Keywords：

Antipsychotic drug; Psychopath; Leptin gene; Weight gain; Polymorphism; Meta-analysis; Case-control study

DOI：

10.7507/1672-2531.20140040

Video：

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Objective To systematically evaluate the relationship between the-2548G/A polymorphism in the leptin gene and antipsychotic-induced weight gain (AIWG). Methods Literature for the relationship between the-2548G/A polymorphism in the leptin gene and AIWG was retrieved in electronic databases including PubMed, EMbase, CNKI and WanFang Data from establishment dates to June, 2013. Two reviewers independently screened studies according to the inclusion and exclusion criteria, extracted data and evaluated the methodological quality of the included studies. Then meta-analysis was performed using RevMan 5.2 software. Results A total of 7 case-control studies were included, involving 404 AIWG cases and 508 controls (patients with no significant changes of weight after taking antipsychotic drugs). The results of meta-analysis showed that, regarding the total population, the-2548G/A polymorphism of the leptin gene was not associated with AIWG (OR=1.16, 95%CI 0.70 to 1.93, P=0.57). After stratification analysis, according to Chinese or non-Chinese origin, the results showed that significant association was found between the-2548G/A polymorphism of leptin gene and AIWG for Chinese (OR=2.15, 95%CI 1.41 to 3.26, P=0.000 4) but not for non-Chinese (OR=0.69, 95%CI 0.45 to 1.07, P=0.10). Conclusion The current evidence suggests that the-2548G/A polymorphism in the leptin gene is associated with increased risk of AIWG for Chinese. Due to limited quantity of the included studies, the aforementioned conclusion needs to be further validate by more high-quality and large-scale studies.

Citation： LUOXue-mei, FANGYun, YANSi-min. Correlation between the-2548G/A Polymorphism of Leptin Gene and Antipsychotic-induced Weight Gain: A Meta-Analysis. Chinese Journal of Evidence-Based Medicine, 2014, 14(2): 231-235. doi: 10.7507/1672-2531.20140040 Copy

1.	Allison DB, Casey DE. Antipsychotic-induced weight gain:a review of the literature. J Clin Psychiatry, 2001, 62(7):22-31.
2.	Weiden PJ, Mackell JA, Mcdonnell DD. Obesity as a risk factor for antipsychotic noncompliance. Schizophr Res, 2004, 66(1):51-57.
3.	梁梅花. Leptin的研究进展.国外医学遗传学分册, 2002, 25(1):16-19.
4.	张崇本, 吴鹤龄.人类单基因肥胖的遗传学基础.遗传学报, 2004, 31(8):864-869.
5.	Li WD, Reed DR, Lee JH, et al. Sequence variants in the 5'-flanking region of the leptin gene are associated with obesity in women. Ann Hum Genet, 1999(63):227-234.
6.	Mammes O, Betoulle D, Aubert R, et al. Association of the G-2548A polymorphism in the 5' region of the LEP gene with overweight. Ann Hum Genet, 2000, 64(5):391-394.
7.	Mammès O, Betoulle D, Aubert R, et al. Novel polymorphisms in the 5' region of the LEP gene:association with leptin levels and response to low-calorie diet in human obesity. Diabetes, 1998, 47(3):487-489.
8.	Le Stunff C, Le Bihan C, Schork NJ, et al. A common promoter variant of the leptin gene is associated with changes in the relationship between serum leptin and fat mass in obese girls. Diabets, 2000, 49(12):2196-2200.
9.	Hoffstedt J, Eriksson P, Mottagui-Tabar S, et al. A polymorphism in the leptin promoter region(-2548 G/A) influences gene expression and adipose tissue secretion of leptin. Horm Metab Res, 2002, 34(7):355-359.
10.	Little J, Higgins JP, Loannidis JP, et al. Strengthening the reporting of genetic association studies(STREGA):an extension of the STROBE Statement. Hum Genet, 2009, 125(2):131-151.
11.	Gregoor JG, van der Weide J, Mulder H, et al. Polymorphisms of the LEP-and LEPR gene and obesity in patients using antipsychotic medication. J Clin Psychopharmacol, 2009, 29(1):21-25.
12.	Kang SG, Lee HJ, Park YM, et al. Possible association between the-2548A/G polymorphism of the leptin gene and olanzapineinduced weight gain. Prog Neuropsychopharmacol Biol Psychiatry, 2008, 32(1):160-163.
13.	Opgen-Rhein C, Brandl EJ, Müller DJ, et al. Association of HTR2C, but not LEP or INSIG2, genes with antipsychotic-induced weight gain in a German sample. Pharmacogenomics, 2010, 11(6):773-780.
14.	Wu R, Zhao J, Shao P, et al. Genetic predictors of antipsychoticinduced weight gain:a case-matched multi-gene study. Zhong Nan Da Xue Xue Bao Yi Xue Ban, 2011, 36(8):720-723.
15.	Yevtushenko OO, Cooper SJ, O'Neill R, et al. Influence of 5-HT2C receptor and leptin gene polymorphisms, smoking and drug treatment on metabolic disturbances in patients with schizophrenia. Br J Psychiatry, 2008, 192(6):424-428.
16.	Zhang ZJ, Yao ZJ, Mou XD, et al. Association of-2548G/A functional polymorphism in the promoter region of leptin gene with antipsychotic agent-induced weight gain. Zhonghua Yi Xue Za Zhi, 2003, 83(24):2119-2123.
17.	牟晓东, 张志珺, 张向荣, 等.瘦素基因启动子区-2548G/A功能多态性与抗精神病药源性肥胖的核心家系关联研究.中南大学学报, 2008, 33(4):316-320.
18.	Miller BJ, Paschall CB, Svendsen DP. Mortality and medical comorbidity among patients with serious mental illness. Psychiatr Serv, 2006, 57(10):1482-1487.
19.	Brandl EJ, Frydrychowicz C, Tiwari AK, et al. Association study of polymorphisms in leptin and leptin receptor genes with antipsychotic-induced body weight gain. Prog Neuropsychopharmacology Biol Psychiatry, 2012, 38(2):134-141.
20.	Templeman LA, Reynolds GP, Arranz B, et al. Polymorphisms of the 5-HT2C receptor and leptin genes are associated with antipsychotic drug-induced weight gain in Caucasian subjects with a firstepisode psychosis. Pharmacogenet Genomics, 2005, 15(4):195-200.

1. Allison DB, Casey DE. Antipsychotic-induced weight gain:a review of the literature. J Clin Psychiatry, 2001, 62(7):22-31.
2. Weiden PJ, Mackell JA, Mcdonnell DD. Obesity as a risk factor for antipsychotic noncompliance. Schizophr Res, 2004, 66(1):51-57.
3. 梁梅花. Leptin的研究进展.国外医学遗传学分册, 2002, 25(1):16-19.
4. 张崇本, 吴鹤龄.人类单基因肥胖的遗传学基础.遗传学报, 2004, 31(8):864-869.
5. Li WD, Reed DR, Lee JH, et al. Sequence variants in the 5'-flanking region of the leptin gene are associated with obesity in women. Ann Hum Genet, 1999(63):227-234.
6. Mammes O, Betoulle D, Aubert R, et al. Association of the G-2548A polymorphism in the 5' region of the LEP gene with overweight. Ann Hum Genet, 2000, 64(5):391-394.
7. Mammès O, Betoulle D, Aubert R, et al. Novel polymorphisms in the 5' region of the LEP gene:association with leptin levels and response to low-calorie diet in human obesity. Diabetes, 1998, 47(3):487-489.
8. Le Stunff C, Le Bihan C, Schork NJ, et al. A common promoter variant of the leptin gene is associated with changes in the relationship between serum leptin and fat mass in obese girls. Diabets, 2000, 49(12):2196-2200.
9. Hoffstedt J, Eriksson P, Mottagui-Tabar S, et al. A polymorphism in the leptin promoter region(-2548 G/A) influences gene expression and adipose tissue secretion of leptin. Horm Metab Res, 2002, 34(7):355-359.
10. Little J, Higgins JP, Loannidis JP, et al. Strengthening the reporting of genetic association studies(STREGA):an extension of the STROBE Statement. Hum Genet, 2009, 125(2):131-151.
11. Gregoor JG, van der Weide J, Mulder H, et al. Polymorphisms of the LEP-and LEPR gene and obesity in patients using antipsychotic medication. J Clin Psychopharmacol, 2009, 29(1):21-25.
12. Kang SG, Lee HJ, Park YM, et al. Possible association between the-2548A/G polymorphism of the leptin gene and olanzapineinduced weight gain. Prog Neuropsychopharmacol Biol Psychiatry, 2008, 32(1):160-163.
13. Opgen-Rhein C, Brandl EJ, Müller DJ, et al. Association of HTR2C, but not LEP or INSIG2, genes with antipsychotic-induced weight gain in a German sample. Pharmacogenomics, 2010, 11(6):773-780.
14. Wu R, Zhao J, Shao P, et al. Genetic predictors of antipsychoticinduced weight gain:a case-matched multi-gene study. Zhong Nan Da Xue Xue Bao Yi Xue Ban, 2011, 36(8):720-723.
15. Yevtushenko OO, Cooper SJ, O'Neill R, et al. Influence of 5-HT2C receptor and leptin gene polymorphisms, smoking and drug treatment on metabolic disturbances in patients with schizophrenia. Br J Psychiatry, 2008, 192(6):424-428.
16. Zhang ZJ, Yao ZJ, Mou XD, et al. Association of-2548G/A functional polymorphism in the promoter region of leptin gene with antipsychotic agent-induced weight gain. Zhonghua Yi Xue Za Zhi, 2003, 83(24):2119-2123.
17. 牟晓东, 张志珺, 张向荣, 等.瘦素基因启动子区-2548G/A功能多态性与抗精神病药源性肥胖的核心家系关联研究.中南大学学报, 2008, 33(4):316-320.
18. Miller BJ, Paschall CB, Svendsen DP. Mortality and medical comorbidity among patients with serious mental illness. Psychiatr Serv, 2006, 57(10):1482-1487.
19. Brandl EJ, Frydrychowicz C, Tiwari AK, et al. Association study of polymorphisms in leptin and leptin receptor genes with antipsychotic-induced body weight gain. Prog Neuropsychopharmacology Biol Psychiatry, 2012, 38(2):134-141.
20. Templeman LA, Reynolds GP, Arranz B, et al. Polymorphisms of the 5-HT2C receptor and leptin genes are associated with antipsychotic drug-induced weight gain in Caucasian subjects with a firstepisode psychosis. Pharmacogenet Genomics, 2005, 15(4):195-200.

Chinese Journal of Evidence-Based Medicine

Correlation between the-2548G/A Polymorphism of Leptin Gene and Antipsychotic-induced Weight Gain: A Meta-Analysis

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