Association of FTO, LEPR and MTHFR Gene Polymorphisms with Metabolic Syndrome in Schizophrenia Patients Receiving Antipsychotics

Abstract

Aim: The occurrence of metabolic syndrome (MS) in schizophrenia patients receiving long-term antipsychotics (APs) contributes to their high mortality rate. We aimed to determine whether genetic polymorphisms of identified candidate genes are associated with MS in our study population. Materials & methods: We recruited 206 schizophrenia patients receiving AP treatment for at least a year. Cross-sectional measurements of weight, height, blood pressure, waist and hip circumference, and other lipid profiles were recorded. Patient DNA was genotyped for 16 candidate gene polymorphisms. Results: Of these patients, 59.7% were found to have MS while 40.3% did not. All metabolic parameters were significantly different between the two groups. Only three of the 16 polymorphisms studied showed significant association with MS; rs9939609 of the FTO gene confers risk for MS (odds ratio [OR]: 1.73, 95% CI: 1.07–2.78, p = 0.026), while rs1137101 of the LEPR gene (OR: 0.47, 95% CI: 0.28–0.80, p = 0.005) and rs1801133 of the MTHFR gene (OR: 0.59, 95% CI: 0.35–0.99, p = 0.049) are protective against MS. Conclusion: Polymorphisms of the FTO, LEPR and MTHFR genes may play a role in MS in Malaysian schizophrenia patients receiving long-term treatment with APs.

Original submitted 29 July 2013; Revision submitted 28 October 2013

KEYWORDS::

• antipsychotics
• FTO rs9939609
• LEPR rs1137101
• metabolic syndrome
• MTHFR rs1801133
• schizophrenia

Authors‘ contributions

Designed the study: MA Said, A Hatim, Z Mohamed, NZ Zainal; conducted the study: SN Roffeei, EHM Mohamed, SA Aida; analyzed the data: SN Roffeei, GP Reynolds; prepared the manuscript: SN Roffeei, GP Reynolds; revised the manuscript: Z Mohamed, GP Reynolds, NZ Zainal.

Financial & competing interests disclosure

This study was funded by the University of Malaya Research Grant (RG214-10HTM, RG270-10HTM), HIR MOHE E00049-20001 and PS196-2010B from the University of Malaya. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This study was funded by the University of Malaya Research Grant (RG214-10HTM, RG270-10HTM), HIR MOHE E00049-20001 and PS196-2010B from the University of Malaya. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.