A customized pigmentation snp array identifies a novel snp associated with melanoma predisposition in the slc45a2 gene
As the incidence of Malignant Melanoma (MM) reflects an interaction between skin colour and UV exposure, variations in genes implicated in pigmentation and tanning response to UV may be associated with susceptibility to MM. In this study, 363 SNPs in 65 gene regions belonging to the pigmentation pat...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2011 |
| País: | España |
| Institución: | Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO) |
| Repositorio: | r-FISABIO. Repositorio Institucional de Producción Científica |
| OAI Identifier: | oai:fisabio.fundanetsuite.com:p8107 |
| Acceso en línea: | https://fisabio.portalinvestigacion.com/publicaciones/8107 https://www.scopus.com/inward/record.uri?eid=2-s2.0-79955772617&doi=10.1371%2fjournal.pone.0019271&partnerID=40&md5=072d5d1e84bc4cc3039cf2280f212d1b |
| Access Level: | acceso abierto |
| Palabra clave: | Adult Aged Aged, 80 and over Antigens, Neoplasm Female Gene Frequency Genetic Predisposition to Disease Genetic Variation Genotype Haplotypes Humans Male Melanoma Membrane Transport Proteins Middle Aged Mutation Oligonucleotide Array Sequence Analysis Polymorphism, Single Nucleotide Risk Spain carrier protein SLC45A2 protein, human tumor antigen ADAMTS20 gene article case control study CKD2 gene controlled study gene gene frequency gene locus gene mutation genetic association genetic predisposition genetic risk genetic susceptibility genetic variability genotype haplotype human major clinical study MC1R gene melanoma nucleotide sequence penetrance pigmentation SILV gene single nucleotide polymorphism SLC45A2 gene TYR gene adult aged DNA microarray female genetics male middle aged mutation risk |
| Sumario: | As the incidence of Malignant Melanoma (MM) reflects an interaction between skin colour and UV exposure, variations in genes implicated in pigmentation and tanning response to UV may be associated with susceptibility to MM. In this study, 363 SNPs in 65 gene regions belonging to the pigmentation pathway have been successfully genotyped using a SNP array. Five hundred and ninety MM cases and 507 controls were analyzed in a discovery phase I. Ten candidate SNPs based on a p-value threshold of 0.01 were identified. Two of them, rs35414 (SLC45A2) and rs2069398 (SILV/CKD2), were statistically significant after conservative Bonferroni correction. The best six SNPs were further tested in an independent Spanish series (624 MM cases and 789 controls). A novel SNP located on the SLC45A2 gene (rs35414) was found to be significantly associated with melanoma in both phase I and phase II (P<0.0001). None of the other five SNPs were replicated in this second phase of the study. However, three SNPs in TYR, SILV/CDK2 and ADAMTS20 genes (rs17793678, rs2069398 and rs1510521 respectively) had an overall p-value <0.05 when considering the whole DNA collection (1214 MM cases and 1296 controls). Both the SLC45A2 and the SILV/CDK2 variants behave as protective alleles, while the TYR and ADAMTS20 variants seem to function as risk alleles. Cumulative effects were detected when these four variants were considered together. Furthermore, individuals carrying two or more mutations in MC1R, a well-known low penetrance melanoma-predisposing gene, had a decreased MM risk if concurrently bearing the SLC45A2 protective variant. To our knowledge, this is the largest study on Spanish sporadic MM cases to date. © 2011 Ibarrola-Villava et al. |
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