Expression of tachykinins and their receptors in plaque psoriasis with pruritus
Expression of tachykinins and their receptors in plaque psoriasis with pruritus
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DOI：
10.1111/j.1365-2133.2011.10241.x
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发表时间：
2011-05-01
影响因子：
10.3
通讯作者：
Nordlind, K.
中科院分区：
文献类型：
--
作者：
Amatya, B.;El-Nour, H.;Nordlind, K.
皮肤黑色素瘤的发病率在世界范围内迅速增加，大约5%的黑色素瘤是遗传性的.在黑色素瘤中检测到染色体1 p36的缺失，但在该区域尚未发现候选的黑色素瘤肿瘤抑制基因。最近，强有力的证据已被报道，CHD 5是一个肿瘤抑制基因在这个region.ObjectivesTo探讨CHD 5参与在familial melanoma.MethodsPeripheral blood DNA从47黑色素瘤家族谁不携带突变的任何三个目前公认的黑色素瘤基因，398例散发性黑色素瘤和398个地理匹配nonmelanoma-bearing对照进行了研究。连锁调查，单核苷酸多态性（SNP）基因分型和突变筛查研究进行了CHD 5 locus.ResultsCHD5基因不排除在任何家庭的连锁分析。在SNP基因分型中，发现CHD 5 rs7513548 SNP与散发性黑色素瘤显著相关（比值比1中心点53，95%置信区间1中心点13-2中心点06）。在208例病例和169名对照中发现了AG基因型（参见。141和175例病例和对照组的AA基因型）。在CHD 5突变筛查中，共检测到50个单碱基替换。其中39个是内含子，11个是外显子。虽然32个是以前识别的变体，但有18个是新发现的。3个，在外显子4，31和32，导致非同义替换。甲p.Met1576Ile的替代被确定在母亲和女儿，都与侵袭性皮肤melanoma.ConclusionsThis研究似乎是第一次报告的CHD 5变异家族性皮肤黑色素瘤。这种CHD 5变体可以阻断或改变CHD 5调节细胞周期途径和实现细胞控制的能力。由于研究的47个家族中只有一个家族有这种变异，这似乎是一种罕见的事件，需要进一步筛查黑色素瘤家族，以确认CHD 5是否参与黑色素瘤发病机制。
P>BackgroundCutaneous melanoma is rapidly increasing in incidence worldwide and approximately 5% of melanomas are hereditary. Deletions in chromosome 1p36 have been detected in melanoma but no candidate melanoma tumour suppressor gene has yet been found in this area. Recently, strong evidence has been reported that CHD5 is a tumour suppressor gene in this region.ObjectivesTo investigate CHD5 involvement in familial melanoma.MethodsPeripheral blood DNA from 47 melanoma families who do not carry mutations in any of the three currently recognized melanoma genes, 398 patients with sporadic melanoma and 398 geographically matched nonmelanoma-bearing controls were studied. Linkage investigation, single nucleotide polymorphism (SNP) genotyping and mutation screening studies were carried out on the CHD5 locus.ResultsThe CHD5 gene was not excluded by linkage analysis in any of the families. On SNP genotyping, the CHD5 rs7513548 SNP was found to be significantly associated with sporadic melanoma (odds ratio 1 center dot 53, 95% confidence interval 1 center dot 13-2 center dot 06). The AG genotype was found in 208 cases and 169 controls (cf. 141 and 175 cases and controls, respectively, for the AA genotype). On CHD5 mutation screening, a total of 50 single-base substitutions were detected. Of these, 39 were intronic and 11 were exonic. While 32 were previously recognized variants, 18 were newly identified. Three, in exons 4, 31 and 32, led to nonsynonymous substitutions. A p.Met1576Ile substitution was identified in a mother and daughter, both with invasive cutaneous melanoma.ConclusionsThis study appears to be the first report of CHD5 variants in familial cutaneous melanoma. Such CHD5 variants could block or alter the ability of CHD5 to regulate the cell cycle pathway and to effect cellular control. As only one of the 47 families studied has this variant, it appears to be a rare event and further screening of melanoma families is required to confirm whether or not CHD5 is involved in melanoma pathogenesis.