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1.
We present two unrelated Japanese pedigrees with achondrogenesis type 1b (ACG1B), characterized by prenatally lethal fetal hydrops and severe micromelia. The affected members in these pedigrees carried a common homozygous missense point mutation in solute carrier family 26 member 2 (SLC26A2), a gene associated with ACG1B (NM_000112:c.1987G>A). This loss‐of‐function point mutation causes substitution of glycine 663 with arginine in a highly conserved loop domain of SLC26A2. Interestingly, only a few cases of this mutation have been registered in Japanese genomic databases, and there are no reports of this mutation in any major genomic databases outside Japan. Furthermore, we confirmed the presence of a homozygous stretch of approximately 75 kb surrounding the pathogenic variant. Our findings suggest that this missense point mutation in SLC26A2, which is likely the cause of the ACG1B phenotypes in these unrelated fetuses, is distributed exclusively in Japan.  相似文献   

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3.
 We report here the identification of 26 single-nucleotide polymorphisms (SNPs) spanning a total of 147 kb in two candidate genes, IL4RA and STAT6, for atopic disorders. Fourteen novel SNPs were found in our population. We also report the identification of three novel polymorphic (CA) repeat regions in these genes. No insertion/deletion polymorphisms in AluY elements were detected. The encoded proteins of these two genes are part of a single signaling pathway, and therefore, functional polymorphisms in these genes could potentially lead to higher risk and susceptibility to atopic disorders. We also examined the allelic frequency and haplotypes of these polymorphisms in a control population. These data will be potentially useful for association studies designed to investigate the role of these genes in atopic disorders such as asthma, eczema, and allergic rhinitis. This is the first report on the polymorphic content of these two genes in the Indian population. Received: August 5, 2002 / Accepted: September 30, 2002  相似文献   

4.
The promoter region of the serotonin transporter gene (SLC6A4) shows a 22-bp tandem repeat polymorphism, indicated as polymorphism C, that has been associated to depression, obsessive-compulsive disorder, memory impairment, and anxiety. Less clear are data regarding its association with Alzheimer's disease (AD). No data were reported regarding its association with questionable dementia (QD). In this study we investigate for polymorphism C in the SLC6A4 gene 302 elderly subjects with a clinical diagnosis of AD (n = 105), QD (n = 88) and no cognitive impairment (n = 114) attending a geriatric ward. A community-dwelling sample of 390 healthy subjects was also included in the analysis. A significant higher prevalence of the C16/C16 genotype in AD than in QD was observed (37.14% vs. 3%; p = 0.041, OR 2.001, 95%CI 1.018–4.024), while no differences in the C16/C14 and C14/C14 genotypes as well as in the estimated allele frequencies were found. No further differences among the three groups of subjects were found, also when they were compared with the community-dwelling sample. These findings suggest that SLC6A4 gene variation may have only a minor role, if any, in AD or QD.  相似文献   

5.
Chemokine receptors (CCR2 and CXCR4) are used as coreceptors for entry of human immunodeficiency virus (HIV) into the target cells. Mutations in CCR2 (CCR2-64I) and stromal-derived factor SDF1 (SDF1-3′A), the primary ligand for CXCR4, exhibited a protective effect against the onset of acquired immune deficiency syndrome (AIDS). The frequency of the SDF1-3′A and CCR2-64I alleles were determined in blood donors from 16 provinces, covering the entire territory of Poland. Of 1063 individuals, 274 (25.8%) were carriers of the SDF1-3′A allele; 36 of them (3.4%) were homozygotes (SDF-3′A/A) while 238 (22.4%) were heterozygotes (SDF-3′G/A), resulting in a 14.6% frequency of the SDF1-3′A allele. Moreover, in the same group of individuals, 234 (22.0%) carried the CCR2-64I allele; 6 of them (0.6%) were homozygotes (CCR2-64I/I), and 228 (21.4%) were heterozygotes (CCR2-64V/I), resulting in an 11.3% frequency of the CCR2-64I allele. The highest frequencies of the SDF1-3′A allele were found in the northeastern provinces and in one of the western provinces of Poland. In contrast, allelic frequencies of CCR2-64I varied slightly among different provinces. The different pattern of prevalence of the SDF1-3′A and CCR2-64I alleles in Poland might suggest that the CCR2-64I allele was spread much earlier than the SDF1-3′A allele in the population of Poland. Received: March 25, 2002 / Accepted: July 29, 2002 Acknowledgments We thank the directors of the Transfusion Centers from the 16 administrative provinces of Poland for providing venous blood samples. This research was supported by grant no. 6PO5B09221 from the State Committee for Scientific Research (KBN) and grant no. 501-1-08-05 from K. Marcinkowski University of Medical Sciences, Poznań. Correspondence to:P.P. Jagodzinski  相似文献   

6.
Deficiency of citrin, liver-type mitochondrial aspartate-glutamate carrier, is an autosomal recessive disorder caused by mutations of the SLC25A13 gene on chromosome 7q21.3 and has two phenotypes: neonatal intrahepatic cholestatic hepatitis (NICCD) and adult-onset type II citrullinemia (CTLN2). So far, we have described 19 SLC25A13 mutations. Here, we report 13 novel SLC25A13 mutations (one insertion, two deletion, three splice site, two nonsense, and five missense) in patients with citrin deficiency from Japan, Israel, UK, and Czech Republic. Only R360X was detected in both Japanese and Caucasian. IVS16ins3kb identified in a Japanese CTLN2 family seems to be a retrotransposal insertion, as the inserted sequence (2,667-nt) showed an antisense strand of processed complementary DNA (cDNA) from a gene on chromosome 6 (C6orf68), and the repetitive sequence (17-nt) derived from SLC25A13 was found at both ends of the insert. All together, 30 different mutations found in 334 Japanese, 47 Chinese, 11 Korean, four Vietnamese and seven non-East Asian families have been summarized. In Japan, IVS16ins3kb was relatively frequent in 22 families, in addition to known mutations IVS11 + 1G > A, 851del4, IVS13 + 1G > A, and S225X in 189, 173, 48 and 30 families, respectively; 851del4 and IVS16ins3kb were found in all East Asian patients tested, suggesting that these mutations may have occurred very early in some area of East Asia.  相似文献   

7.
Crohn disease (CD) is an inflammatory bowel disease characterized by chronic transmural, segmental, and typically granulomatous inflammation of the gut. Recently, two novel candidate gene loci associated with CD, SLC22A4 and SLC22A5 on chromosome 5 known as IBD5 and DLG5 on chromosome 10, were identified through association analysis of Caucasian CD patients. We validated these candidate genes in Japanese patients with CD and found a weak but possible association with both SLC22A4 (P=0.028) and DLG5 (P=0.023). However, the reported genetic variants that were indicated to be causative in the Caucasian population were completely absent in or were not associated with Japanese CD patients. These findings imply significant differences in genetic background with CD susceptibility among different ethnic groups and further indicate some difficulty of population-based studies.  相似文献   

8.

Background

Primary biliary cirrhosis (PBC) is an organ specific autoimmune disease of still unidentified genetic etiology. We have shown that endothelins (ETs), produced by the liver endothelial cells are increased in PBC and may play a major pathogenetic role.

Aims

To study gene polymorphisms related to the endothelial cells (eNOS, EDN-1 genes) and, to investigate whether the previously reported association of CTLA4 gene polymorphisms is replicated in a genetically homogeneous Greek population.

Patients and methods

Genomic DNA was extracted from 100 PBC patients (83 females, 93% AMA+, 74/100 Ludwig stage I–II) and 158 healthy controls. eNOS, CTLA4 and ET1 polymorphisms were determined by PCR–RFLPs analysis.

Results

Both eNOS intron4 VNTR and eNOS exon7 G894T SNP were significantly associated with increased risk in PBC. EDN-11 rs2071942 “A” and rs5370 “T” alleles appeared a tendency for association with disease progression. No association was found between PBC and the CTLA4 SNPs analyzed.

Conclusions

We demonstrated that eNOS, a gene related to the liver endothelium function is associated with PBC. Contrarily, the important in adaptive immunity gene CTLA4 was not associated with the disease in the homogeneous population analyzed. These results are compatible partially with our previous hypothesis that defects of the liver endothelial system, leading to endothelin overproduction, may be a fundamental early pathogenetic mechanism in PBC.  相似文献   

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