| 1 | Genet. Med. 2010 Oct 12: 641-7 |
|---|---|
| PMID | 20808231 |
| Title | Recurrent 200-kb deletions of 16p11.2 that include the SH2B1 gene are associated with developmental delay and obesity. |
| Abstract | The short arm of chromosome 16 is rich in segmental duplications, predisposing this region of the genome to a number of recurrent rearrangements. Genomic imbalances of an approximately 600-kb region in 16p11.2 (29.5-30.1 Mb) have been associated with autism, intellectual disability, congenital anomalies, and schizophrenia. However, a separate, distal 200-kb region in 16p11.2 (28.7-28.9 Mb) that includes the SH2B1 gene has been recently associated with isolated obesity. The purpose of this study was to better define the phenotype of this recurrent SH2B1-containing microdeletion in a cohort of phenotypically abnormal patients not selected for obesity. Array comparative hybridization was performed on a total of 23,084 patients in a clinical setting for a variety of indications, most commonly developmental delay. Deletions of the SH2B1-containing region were identified in 31 patients. The deletion is enriched in the patient population when compared with controls (P = 0.003), with both inherited and de novo events. Detailed clinical information was available for six patients, who all had developmental delays of varying severity. Body mass index was ?95th percentile in four of six patients, supporting the previously described association with obesity. The reciprocal duplication, found in 17 patients, does not seem to be significantly enriched in our patient population compared with controls. Deletions of the 16p11.2 SH2B1-containing region are pathogenic and are associated with developmental delay in addition to obesity. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | J Clin Psychopharmacol 2015 Oct 35: 574-8 |
| PMID | 26263223 |
| Title | The Relationships of Obesity-Related Genetic Variants With Metabolic Profiles and Response to Metformin in Clozapine-Treated Patients With Schizophrenia. |
| Abstract | Obesity-related genetic variants, including TMEM18 (rs6548238), SH2B1 (rs7498665), and GNPDA2 (rs10938397), have been shown to be associated with obesity in the general population. Our study aimed to test whether these genetic variants are associated with metabolic profiles and metformin treatment response in clozapine-treated schizophrenic patients. We recruited 107 clozapine-treated patients who were genotyped and measured their metabolic profiles. Fifty-five subjects, who had at least 1 metabolic abnormality in a range of measures, were subsequently randomized to a 24-week trial of metformin (n = 28) or placebo (n = 27). We examined the associations between TMEM18, SH2B1, GNPDA2 genetic variants and metabolic profiles at baseline in all patients and metabolic changes in the trial groups. We found a significant association between SH2B1 and blood pressure at baseline in all patients. In the metformin group, TMEM18 minor allele carriers had a greater reduction in insulin levels (P = 0.04). A significantly higher proportion of TMEM18 and GNPDA2 minor allele carriers (60% and 40%) lost more than 7% of their body weight after metformin treatment as compared with their homozygous counterparts (21.7% and 15.4%, P = 0.02 and 0.004, respectively).There were trends toward favorable metabolic changes in minor allele carrier groups. In the placebo group, no association between genetic variants and changes in metabolic profiles was found. In conclusion, the study results suggest that these genes might be associated with metabolic abnormalities and response to metformin in clozapine-treated patients with schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | J Clin Psychopharmacol 2015 Oct 35: 574-8 |
| PMID | 26263223 |
| Title | The Relationships of Obesity-Related Genetic Variants With Metabolic Profiles and Response to Metformin in Clozapine-Treated Patients With Schizophrenia. |
| Abstract | Obesity-related genetic variants, including TMEM18 (rs6548238), SH2B1 (rs7498665), and GNPDA2 (rs10938397), have been shown to be associated with obesity in the general population. Our study aimed to test whether these genetic variants are associated with metabolic profiles and metformin treatment response in clozapine-treated schizophrenic patients. We recruited 107 clozapine-treated patients who were genotyped and measured their metabolic profiles. Fifty-five subjects, who had at least 1 metabolic abnormality in a range of measures, were subsequently randomized to a 24-week trial of metformin (n = 28) or placebo (n = 27). We examined the associations between TMEM18, SH2B1, GNPDA2 genetic variants and metabolic profiles at baseline in all patients and metabolic changes in the trial groups. We found a significant association between SH2B1 and blood pressure at baseline in all patients. In the metformin group, TMEM18 minor allele carriers had a greater reduction in insulin levels (P = 0.04). A significantly higher proportion of TMEM18 and GNPDA2 minor allele carriers (60% and 40%) lost more than 7% of their body weight after metformin treatment as compared with their homozygous counterparts (21.7% and 15.4%, P = 0.02 and 0.004, respectively).There were trends toward favorable metabolic changes in minor allele carrier groups. In the placebo group, no association between genetic variants and changes in metabolic profiles was found. In conclusion, the study results suggest that these genes might be associated with metabolic abnormalities and response to metformin in clozapine-treated patients with schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |