Polymorphisms of the LEP , LEPR and HTR2C Gene: Obesity and BMI Change in Patients Using Antipsychotic Medication in a Naturalistic Setting

Abstract

The LEPR Q223R polymorphism may be a risk factor for obesity in women with a psychotic disorder treated with atypical antipsychotic drugs. This is in line with earlier findings of our group.

Genetics of Common Antipsychotic-Induced Adverse Effects

“…Several studies included in our results have replicated the association of -759C/T with AIWG [42,43,44,45,46], though negative and contradictory results were also reported [47,48,49,50,51,52,53,54]. One study involving a heterogeneous psychiatric sample reported that carriers of the HTR2C -759T allele were protected against the weight-inducing effects of olanzapine [42].…”

“…Taken together, there is a sound theoretical basis supporting the potential involvement of LEP and LEPR in AP-induced metabolic dysregulation. Indeed, several studies from our review have implicated these genes in metabolic AAEs [46,52,72,73,74,75]. Still, negative and contradictory results have also been reported [44,62,76,77].…”

“…Kang et al [50] also reported a trend in their study involving a sample of Korean SCZ patients. Five other studies reported neither an association nor a trend [51,52,53,54,55]. As Wallace et al [41] first pointed out, contradictory reports relating to this association can mainly be attributed to differences in study duration, as the relationship between AIWG and -759C/T is most prominent during the early stages of treatment (<3 months).…”

“…Another study by Gregoor et al [52] found that baseline obesity risk was significantly greater for females carrying the LEPR 223R allele. This result runs contrary to the finding from their 2009 study which instead reported that the 223R allele was associated with lower baseline risk for female obesity [78].…”

Mechanisms of development of antipsychotic-induced metabolic disorders: pharmacogenetic aspect

“…По данным отдель-ных авторов, аллельные варианты AA гена LEP 2548 G/A ассоциированы с набором веса [80][81][82]. В то же время вышли публикации, указывающие на отсутствие взаимосвязи межу ОНП 2548G/A гена LEP и метаболическими нарушениями [83]. Несмотря на предполагаемое важное значение нейропетида Y в механизме регуляции пищевого поведения, достоверных исследований, показы-вающих влияние полиморфности генов данного фактора не так много.…”