Table 1.
Summary of cross-sectional studies examining the association of leptin polymorphisms and metabolic disturbances in antipsychotic use.
| Author (year) | n (% male) | Population/ diagnosis |
Medications | Dose | Treatment duration |
SNP(s) studied | Summary of results | Ref. |
|---|---|---|---|---|---|---|---|---|
| Ruano et al (2007) | 168(66) | Caucasian (84%) African–American (14%) Diagnoses not reported† | Olanzapine Risperidone | Not available | Patients already on AP; duration unknown | LEPR rs7602 rs1171276 N656K‡ rs8179183 | Significant association between LEPR N656K (rsS179183) and weight in risperidone-treated patients only; G allele carriers were protected against higher weight | [91] |
| Yevtushenko et al. (2008) | 134(65) | Schizophrenia and schizoaffective disorder | Olanzapine Clozapine Risperidone | Not available | Unknown duration of AP exposure | LEP −2548G/A (rs7799039) HTR2C −759C/T (rs3813929) | Among subjects with the HTR2C −759C/CC genotype, those with LEP −2548 G allele versus AA homozygotes had higher BMI, larger waist circumference and presence of metabolic syndrome (BMI 29.89 ± 6.66 kg/m2 vs 26.09 ± 5.53 kg/m2; p = 0.021 waist circumference: 103.86 ±15.61 cm vs 93.78 ± 16.00 cm; p = 0.012: metabolic syndrome 33 patients vs two patients; p = 0.003) | [92] |
| Gregoor et al (2009)§ | 200 (67) | Caucasian Schizophrenia, schizoaffective and other psychotic disorders | Clozapine Olanzapine Risperidone Other unspecified | Not available | At least 3 months | LEP −2548G/A (rs7799039) | No significant association with obesity | [93] |
| LEPR Q223R‡ (rs1137101) | Female QQ homozygotes had higher rate of obesity (defined as BMI >30 kg/m2) versus R carriers (70.6% obese in QQ vs 38.5% in QR; p = 0.007: vs 40% in RR; p = 0.018) | |||||||
| Gregoor et al (2010)§ | 200 (67) | Caucasian Schizophrenia, schizoaffective and other psychotic disorders | Clozapine Olanzapine Risperidone Other unspecified | Not available | At least 3 months | LEP −2548G/A (rs7799039) HTR2C −759C/T (rs3813929) | Combined absence of HTR2C T allele and presence of LEP-2548G allele associated with obesity in persons without an HTR2C T allele (33.9% of subjects vs 22.2% in other genotype groups; OR: 2.88; 95% CI: 1.05–7.95) | [94] |
| LEPR Q223R (rs1137101) HTR2C −759C/T (rs3813929) | No significant association with obesity | |||||||
| Opgen-Rhein et al. (2010)¶ | 128(62.5) | European (92%) Turkish (8%) Schizophrenia and schizoaffective disorder | Olanzapine Clozapine Risperidone Amisulpride Quetiapine Clozapine Some FGAs | Not available | At least 6 weeks | LEP −2548G/A (rs7799039) HTR2C −759C/T (rs3813929) | No significant association with clinically significant weight gain (>7% initial bodyweight) after 6 weeks | [95] |
| Fernandez et al (2010) | 56(78.6) | Schizophrenia | Clozapine | Not available | At least 3 months | LEP −2S48G/A (rs7799039) LEPR Q223R† (rs1137101) | No association between LEP and LEPR variants and frequency of metabolic syndrome or obesity when comparing homozygotes for LEP −2548 GG versus A allele carriers and LEPR 223 QQ vs R allele carriers in all subjects. LEPR 223 QQ genotype was associated with lower triglyceride levels in males after controlling for dose | [96] |
| Moons et al (2011) | 261 (68.6) | Schizophrenia and schizoaffective disorder | Risperidone Olanzapine Clozapine Quetiapine Amisulpride Aripiprazole | Not available | At least 3 months | LEPR N656K‡ (rs8179183) | No association found with LEPR N656K genotype and weight, BMI, waist circumference, hip circumference or waist:hip ratio | [97] |
†
Participants recruited from hospitals treating severe, persistent mental illness.
‡
LEPR Q223R (rs1137101) polymorphism: G allele codes for R (arginine), A allele codes for Q (glutamine); LEPR N656K (rs8179183) polymorphism: C allele codes for N (asparagine), G allele codes for K (lysine).
§
Both studies by Gregoor et al. utilized the same subject population.
¶
Case-control, retrospective study.
AP: Antipsychotic; FGA: First-generation antipsychotic; OR: Odds ratio.