To determine if neuregulin 1 (NRG1) is associated with schizophrenia in Asian populations, we investigated a Han Chinese population using both a family trio design and a case-control design. A total of 25 microsatellite markers and single nucleotide polymorphisms (SNPs) were genotyped spanning the 1.1 Mb NRG1 gene including markers of a seven-marker haplotype at the 5 0 end of the gene found to be in excess in Icelandic and Scottish schizophrenia patients. The alleles of the individual markers forming the seven marker at-risk haplotype are not likely to be causative as they are not in excess in patients in the Chinese population studied here. However using unrelated patients, we find a novel haplotype (HAP China 1 ), immediately upstream of the Icelandic haplotype, in excess in patients (11.9% in patients vs 4.2% in controls; P ¼ 0.0000065, risk ratio (rr) 3.1), which was not significant when parental controls were used. Another haplotype (HAP China 2 ) overlapping the Icelandic risk haplotype was found in excess in the Chinese (8.5% of patients vs 4.0% of unrelated controls; P ¼ 0.003, rr 2.2) and was also significant using parental controls only (P ¼ 0.0047, rr 2.1). A four-marker haplotype at the 3 0 end of the NRG1 gene, HAP China 3 , was found at a frequency of 23.8% in patients and 13.7% in nontransmitted parental haplotypes (P ¼ 0.000042, rr ¼ 2.0) but was not significant in the case-control comparison. We conclude that different haplotypes within the boundaries of the NRG1 gene may be associated with schizophrenia in the Han Chinese. Keywords: 8p; linkage; glial growth factor; psychosis; genetics; transmission; family Schizophrenia is a debilitating brain disease that affects up to 1% of the population worldwide. There is no cure, and treatments, which are mainly based on antagonism of dopamine, serotonin and other neurotransmitter receptors in the brain, are only partially effective. Although the aetiology of schizophrenia is not well understood, there is longstanding evidence of a genetic component, and recent twin studies place the heritability of schizophrenia at more than 80%. 1 Despite this high heritability, numerous candidate gene association studies have failed to identify susceptibility genes clearly. There are a variety of reasons for this failure, including probable locus and aetiological heterogeneity, characterised by the probable existence of numerous genes of small effect, the involvement of several biological pathways, lack of a pathophysiology to help with the selection of candidate genes, and methodological difficulties related to study design, statistical power and diagnostic validity and reliability.2 Linkage analysis has been more successful, with good evidence for genetic loci identified on chromosomes 8p, 22q, 13q and several other locations in the genome.3,4 These linkage findings have led to systematic genetic mapping efforts and positional candidate gene analysis of these loci. 5In a recent publication by Stefansson et al, 6 linkage to chromosome 8p followed by haplotype mappin...

The dystrobrevin-binding protein 1 (DTNBP1) gene on chromosome 6p has emerged as a potential susceptibility gene for schizophrenia. Although a number of attempts to replicate the original association finding have been successful, they have not identified any obvious pathogenic variants or a single at risk haplotype common to all populations studied. In the present study we attempted further replication in an independent sample of 638 nuclear families from the Han Chinese population of Sichuan Province, SW China. We also examined 580 Scottish schizophrenic cases and 620 controls. We genotyped 10 single-nucleotide polymorphisms (SNPs) in DTNBP1 that were used in the original report of association, plus rs2619538 (SNP 'A') in the putative promoter region, which has also been associated with schizophrenia. In the Chinese trios we found that two SNPs (P1635 and P1765) were significantly overtransmitted, but with alleles opposite to those reported in the original studies. SNPs P1757 and P1765 formed a common haplotype, which also showed significant overtransmission. In the Scottish cases and controls, no individual markers were significantly associated with schizophrenia. A single haplotype, which included rs2619538 and P1583, and one rare haplotype, composed of P1320 and P1757, were significantly associated with schizophrenia, but no previously reported haplotypes were associated. Based on the data from the Chinese population, our results provide statistical support for DTNBP1 as a susceptibility gene for schizophrenia, albeit with haplotypes different from those of the original study. However, our lack of replication in the Scottish samples also indicates that caution is warranted when evaluating the robustness of the evidence for DTNBP1 as genetic risk factor for schizophrenia. Molecular Psychiatry (2005Psychiatry ( ) 10, 1037Psychiatry ( -1044Psychiatry ( . doi:10.1038 published online 26 July 2005 Keywords: psychosis; association; 6p; dysbindin; dystrobrevin Schizophrenia is a debilitating brain disease that affects up to 1% of the population worldwide. There is no cure and treatments, which are mainly based on antagonism of dopamine, serotonin and other neurotransmitter receptors in the brain, are only partially effective. Although the aetiology of schizophrenia is not well understood, there is longstanding evidence of a genetic component, and recent twin studies place the heritability of schizophrenia at more than 80%.

The present study partially confirmed the previous findings, suggesting that the ApoCI A allele might contribute to the susceptibility to moderate to severe sporadic AD in Chinese.

Background Gastric adenosquamous carcinoma (gasc) is a rare entity with distinctive characteristics that are not fully understood. In the present study, we evaluated the characteristics of this rare disease. Methods The U.S. Surveillance, Epidemiology, and End Results program database was searched to determine the clinicopathologic features, prognostic factors, and treatments for 246 patients with gasc and 42,735 patients with gastric adenocarcinoma (gac). Results Relative to gac, gasc is associated with higher proportions of cardia involvement, high-grade tumours, deep tumour invasion, metastatic lymph nodes, and chemotherapy treatment. In patients who underwent potentially curative surgery (pcs), gasc was associated with a higher proportion of radiotherapy use and poorer overall survival (p < 0.001), although no significant difference (p = 0.802) was observed after propensity score matching (psm). Multi­variate analysis after psm revealed that the independent prognostic factors for gasc were TNM stage [hazard ratio (hr): 1.512; p = 0.021] and regional nodes examined (hr: 0.588; p = 0.02). In patients with advanced disease, no significant difference in survival between gasc and gac was observed (p = 0.212), although survival was significantly poorer for gasc after psm (p = 0.019). Multivariate analysis after psm revealed that the independent prognostic factors for gasc were invasion depth (hr: 1.303; p = 0.036) and chemotherapy (hr: 0.444; p < 0.001). Conclusions Relative to gac, gasc was associated with more aggressive features, although survival outcomes were similar after pcs. Chemotherapy remains a mainstay of treatment for patients with advanced gasc, but its role remains unclear for patients who are undergoing pcs.

Neuroendocrine neoplasms of the pancreas, previously called islet cell tumours, are rare with an annual incidence of 2-4/million population. One classification includes low-grade neuroendocrine tumours, intermediate-grade neuroendocrine tumours and neuroendocrine carcinomas. A second issue is whether the tumours produce hormones that result in hormonal syndromes ( functioning or non-functioning tumors). In recent series, the majority (50-75%) have been non-functioning. When the tumours are functioning, there can be hypersecretion of a variety of hormones, including insulin (insulinomas), gastrin (gastrinomas), glucagon (glucagonomas), vasoactive intestinal peptide (VIPomas) and somatostatin (somatostatinomas). Non-functioning pancreatic neuroendocrine tumours may also secrete substances such as chromogranins, neuron-specific enolase, pancreatic polypeptide and ghrelin but these do not present clinically with hormonal syndromes. The most common sites for metastases at presentation are local lymph nodes (25%) and liver (25%). The rate of growth of neuroendocrine tumors is highly variable. Some tumors show no or minimal growth over several years while others are rapidly progressive. Prognostic factors include the presence of metastases, the size of the primary tumor, histological features and perhaps hormone secretion. The patient illustrated below was unusual because of pelvic metastases and the presence of Cushings syndrome.A woman, aged 27, was admitted to our hospital with polydipsia, limb weakness, hirsutism and fasting hyperglycaemia for six months and amenorrhoea for two months. Blood tests revealed an elevated fasting blood glucose (10.8 mmol/L) and a low serum potassium (2.3 mmol/L). Hormone studies revealed an elevated plasma cortisol (8:00am > 1750 nmol/L), an elevated 24 hour urinary free cortisol (2762 μg) and an elevated level of adrenocorticotropic hormone (ACTH, 101 ng/L). Cortisol secretion was not affected by a high dose of dexamethasone. A computed tomography scan revealed a relatively large mass in the body and tail of the pancreas (Figure 1). The tumour invaded the splenic vein and, in addition, nodules were detected in the pelvis and both ovaries (Figure 2, above). A partial pancreatectomy, splenectomy, hysterectomy, bilateral oophorectomy and excision of pelvic and ovarian tumour nodules were performed. Immunohistochemical studies showed that the tumour was positive for synaptophysin, chromogranin A and ACTH. The histological appearance of the ovarian metastases in shown in Figure 2 (below). The final diagnosis was a pancreatic neuroendocrine tumour of intermediategrade with pelvic and bilateral ovarian metastases. After the operation, cortisol and ACTH levels returned to normal. In some studies, ectopic ACTH production has been an adverse prognostic feature.