A comprehensive analysis of mitochondrial genes variants and their association with antipsychotic-induced weight gain

作者：Mittal Kirti; Goncalves Vanessa F^*; Harripaul Ricardo; Cuperfain Ari B; Rollins Brandi; Tiwari Arun K; Zai Clement C; Maciukiewicz Malgorzata; Muller Daniel J; Vawter Marquis P; Kennedy James L

来源：Schizophrenia Research, 2017, 187: 67-73.

DOI：10.1016/j.schres.2017.06.046

• Mitochondria
• Mitochondrial DNA variants
• Nuclear-encoded mitochondrial genes
• Schizophrenia
• Antipsychotic-induced weight gain
• Next generation sequencing

Antipsychotic Induced Weight Gain (AIWG) is a common and severe side effect of many antipsychotic medications. Mitochondria play a vital role for whole-body energy homeostasis and there is increasing evidence that antipsychotics modulate mitochondrial function. This study aimed to examine the role of variants in nuclear-encoded mitochondrial genes and the mitochondrial DNA (mtDNA) in conferring risk for AIWG. We selected 168 European-Caucasian individuals from the CATIE sample based upon meeting criteria of multiple weight measures while taking selected antipsychotics (risperidone, quetiapine or olanzapine). We tested the association of 670 nuclear-encoded mitochondrial genes with weight change (%) using MAGMA software. Thirty of these genes showed nominally significant P-values (<0.05). We were able to replicate the association of three genes, CLPB, PARL, and ACAD10, with weight change (%) in an independent prospectively assessed AIWG sample. We analyzed mtDNA variants in a subset of 74 of these individuals using next-generation sequencing. No common or rare mtDNA variants were found to be significantly associated with weight change (%) in our sample. Additionally, analysis of mitochondrial haplogroups showed no association with weight change (%). In conclusion, our findings suggest nuclear-encoded mitochondrial genes play a role in AIWG. Replication in larger sample is required to validate our initial report of mtDNA variants in AIWG.

• 出版日期2017-9
• 单位河北医科大学