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Although the association between the Ser9Gly polymorphism of the dopamine D3 receptor gene (DRD3) and schizophrenia has been investigated by many research groups, it is not known whether the Ser9Gly polymorphism alone or a variation in linkage disequilibrium may effect susceptibility to schizophrenia. We searched the 5Ј region of the DRD3 gene and found three novel polymorphisms: −712G/C, −205A/G, and Ala38Thr. The Ala38Thr polymorphism is located in the first transmembrane region and is conserved in the monkey, mouse, and rat. Case-control comparisons in 153 Japanese schizophrenia patients and 122 Japanese controls did not suggest an association between Ala38Thr and schizophrenia. However, there was a marginally significant association between the Ser9 allele of the Ser9Gly polymorphisms and schizophrenia (P = 0.02). Furthermore, there was a highly significant association between haplotypes of the −712G/C, −205A/G, and Ser9Gly polymorphisms and schizophrenia (P = 0.0007, corrected P = 0.007). These positive findings were replicated in an additional 99 Japanese schizophrenia patients and 132 controls (P = 0.04 and 0.0004, respectively). The most allelic differences of the Ser9Gly polymorphism between patient and control groups arose from the chromosome carrying specific alleles of the other three polymorphisms. This study indicates unknown variant(s) in linkage disequilibrium with the DRD3 haplotypes associated with schizophrenia. Molecular Psychiatry (2000) 5, 433-438.Several lines of evidence suggest that the dopamine D3 receptor is involved in the pathophysiology of schizophrenia. The D3 receptor has a restricted pattern of expression in brain limbic areas associated with cognitive function and motivated behavior. 1 It may mediate the pharmacological effects of antipsychotic drugs, since typical and atypical antipsychotic drugs have a relatively high affinity for the dopamine D3 receptor. 2 Postmortem studies suggest a selective loss of DRD3 mRNA in parietal and motor cortical regions of patients with chronic schizophrenia. 3 D3 selective agonists and antagonists reveal an inhibitory role on motor behavior for the D3 receptor, opposite to that of the D2 receptor. Tolerance to the motor but not to the therapeutic effects of neuroleptics is observed after prolonged treatment, which up-regulate D2 but not D3 receptor levels in animals. 4 A genetic association between the Ser9Gly polymorphism of the dopamine D3 receptor gene (DRD3) and schizophrenia has been investigated by many researchers. Groups in the UK and France found an association between homozygosity of this polymorphism and schizophrenia. 5 Some studies imply that a disproportionate frequency of homozygosity may be pronounced in patients with a family history of schizophrenia 6 and in patients with a good response to neuroleptics. 7 Although many researchers reported negative findings in unselected samples, 7-15 a meta-analysis of over 30 case-control studies resulted in a higher frequency of both forms of the homozygote in schizophrenia patients than ...

These results suggest that decreased ATP2B1 gene expression is associated with impaired endothelial NOS activity and nitric oxide production, and the ATP2B1 gene plays a crucial role in the regulation of blood pressure.

BackgroundTolvaptan, a vasopressin V2 receptor blocker, has a diuretic effect for patients with heart failure. However, there were a few data concerning the effects of tolvaptan in patients with chronic kidney disease (CKD).MethodsWe retrospectively analyzed 21 patients with chronic heart failure and CKD. Tolvaptan was co-administered with other diuretics in-use, every day. We compared clinical parameters before and after the treatments with tolvaptan. Furthermore, we examined the correlations between baseline data and the change of body weight.ResultsTolvaptan decreased the body weight and increased the urine volume (p = 0.001). The urine osmolality significantly decreased throughout the study period. Urinary Na/Cr ratio and FENa changed significantly after 4 h, and more remarkable after 8 h (p = 0.003, both). Serum creatinine increased slightly after 1 week of treatment (p = 0.012). The alteration of body weight within the study period correlated negatively with the baseline urine osmolality (r = −0.479, p = 0.038), the baseline urine volume (r = −0.48, p = 0.028), and the baseline inferior vena cava diameter (IVCD) (r = −0.622, p = 0.017). Hyponatremia was improved to the normal value, and the augmentations of the sodium concentration were negatively associated with the basal sodium levels (p = 0.01, r = −0.546).ConclusionsTolvaptan is effective in increasing diuresis and improved hyponatremia, even in patients with CKD. The baseline urine osmolality, urine volume, and IVCD may be useful predictors for diuretic effects of tolvaptan.