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Human Pigmentation (human + pigmentation)
Selected AbstractsGenetic analysis of three important genes in pigmentation and melanoma susceptibility: CDKN2A, MC1R and HERC2/OCA2EXPERIMENTAL DERMATOLOGY, Issue 9 2010Maider Ibarrola-Villava Please cite this paper as: Genetic analysis of three important genes in pigmentation and melanoma susceptibility: CDKN2A, MC1R and HERC2/OCA2. Experimental Dermatology 2010; 19: 836,844. Abstract:, The CDKN2A gene is regarded as the major familial malignant melanoma (MM) susceptibility gene. Human pigmentation is one of the main modulators of individual risk of developing MM. Therefore, the genes involved in the determination of skin colour and tanning response are potentially implicated in MM predisposition and may be useful predictors of MM risk in the general population. The human melanocortin-1 receptor gene (MC1R) plays a crucial role in pigmentation and also appears to be important in MM. The OCA2 gene has emerged as a new and significant determinant of human iris colour variation. We present a case,control study in Spanish population including 390 consecutive patients with melanoma and 254 control subjects. Sequence analysis of the entire coding region and genotyping of 5 tag-SNPs in the genomic region of MC1R was performed. We identified 27 variants, two reaching statistical significance [R160W (OR: 4.18, 95% CI: 1.24,14.04, P = 0.02) and D294H (OR: 3.10, 95% CI: 1.37,7.01, P = 0.01)] and we detected two novel non-synonymous changes: V92L and T308M. Odds ratio for carrying two functional variants was 4.25 (95% CI: 2.30,7.84, P = 3.63 × 10,6). Haplotypes of the entire MC1R region have been established, and we observed an enrichment of a rare European haplotype similar to African values carrying variants V92M and I155T. In addition, three potentially functional SNPs were selected in p16/CDKN2A and in the promoter region of OCA2/HERC2. Our data for CDKN2A gene did not reach statistically significant results for any of the two studied alleles. We found that the variant allele A > G of OCA2/HERC2 (rs12913832) was associated with pigmentation features: eye, hair and skin colour; P -values = 1.8 × 10,29, 9.2 × 10,16, 1.1 × 10,3, respectively, validating previous results. [source] Genetic variants in pigmentation genes, pigmentary phenotypes, and risk of skin cancer in CaucasiansINTERNATIONAL JOURNAL OF CANCER, Issue 4 2009Hongmei Nan Abstract Human pigmentation is a polygenic quantitative trait with high heritability. Although a large number of single nucleotide polymorphisms (SNPs) have been identified in pigmentation genes, very few SNPs have been examined in relation to human pigmentary phenotypes and skin cancer risk. We evaluated the associations between 15 SNPs in 8 candidate pigmentation genes (TYR, TYRP1, OCA2, SLC24A5, SLC45A2, POMC, ASIP and ATRN) and both pigmentary phenotypes (hair color, skin color and tanning ability) and skin cancer risk in a nested case-control study of Caucasians within the Nurses' Health Study (NHS) among 218 melanoma cases, 285 squamous cell carcinoma (SCC) cases, 300 basal cell carcinoma (BCC) cases and 870 common controls. We found that the TYR Arg402Gln variant was significantly associated with skin color (p -value = 7.7 × 10,4) and tanning ability (p -value = 7.3 × 10,4); the SLC45A2 Phe374Leu variant was significantly associated with hair color (black to blonde) (p -value = 2.4 × 10,7), skin color (p -value = 1.1 × 10,7) and tanning ability (p -value = 2.5 × 10,4). These associations remained significant after controlling for MC1R variants. No significant associations were found between these polymorphisms and the risk of skin cancer. We observed that the TYRP1 rs1408799 and SLC45A2 1721 C>G were associated with melanoma risk (OR, 0.77; 95% CI, 0.60,0.98 and OR, 0.75; 95% CI, 0.60,0.95, respectively). The TYR Ser192Tyr was associated with SCC risk (OR, 1.23; 95% CI, 1.00,1.50). The TYR haplotype carrying only the Arg402Gln variant allele was significantly associated with SCC risk (OR, 1.35; 95% CI, 1.04,1.74). The OCA2 Arg419Gln and ASIP g.8818 A>G were associated with BCC risk (OR, 1.50; 95% CI, 1.06,2.13 and OR, 0.73; 95% CI, 0.53,1.00, respectively). The haplotype near ASIP (rs4911414[T] and rs1015362[G]) was significantly associated with fair skin color (OR, 2.28; 95% CI, 1.46,3.57) as well as the risks of melanoma (OR, 1.68; 95% CI, 1.18,2.39) and SCC (OR, 1.54; 95% CI, 1.08,2.19). These associations remained similar after adjusting for pigmentary phenotypes and MC1R variants. The statistical power of our study was modest and additional studies are warranted to confirm the associations observed in the present study. Our study provides evidence for the contribution of pigmentation genetic variants, in addition to the MC1R variants, to variation in human pigmentary phenotypes and possibly the development of skin cancer. © 2009 UICC [source] Interactions Between HERC2, OCA2 and MC1R May Influence Human Pigmentation PhenotypeANNALS OF HUMAN GENETICS, Issue 2 2009Wojciech Branicki Summary Human pigmentation is a polygenic trait which may be shaped by different kinds of gene,gene interactions. Recent studies have revealed that interactive effects between HERC2 and OCA2 may be responsible for blue eye colour determination in humans. Here we performed a population association study, examining important polymorphisms within the HERC2 and OCA2 genes. Furthermore, pooling these results with genotyping data for MC1R, ASIP and SLC45A2 obtained for the same population sample we also analysed potential genetic interactions affecting variation in eye, hair and skin colour. Our results confirmed the association of HERC2 rs12913832 with eye colour and showed that this SNP is also significantly associated with skin and hair colouration. It is also concluded that OCA2 rs1800407 is independently associated with eye colour. Finally, using various approaches we were able to show that there is an interaction between MC1R and HERC2 in determination of skin and hair colour in the studied population sample. [source] A study of a single variant allele (rs1426654) of the pigmentation-related gene SLC24A5 in Greek subjectsEXPERIMENTAL DERMATOLOGY, Issue 2 2009Gerasimos Dimisianos Abstract:, The SLC24A5 gene, the human orthologue of the zebrafish golden gene, has been shown to play a key role in human pigmentation. In this study, we investigate the prevalence of the variant allele rs1426654 in a selected sample of Greek subjects. Allele-specific polymerase chain reaction was performed in peripheral blood samples from 158 attendants of a dermatology outpatient service. The results were correlated with pigmentary traits and MC1R genotype. The vast majority of subjects (99%) were homozygous for the Thr111 allele. Only two subjects from the control group (1.26%) were heterozygous for the alanine and threonine allele. Both of these Thr111/Ala111 heterozygotes carried a single polymorphism of MC1R (one with the V92M variant and another with the V60L variant). Following reports of the rs1426654 polymorphism reaching fixation in the European population, our study of Greek subjects showed a prevalence of the Thr111 allele, even among subjects with darker skin pigmentation or phototype. [source] Melanocortin 1 receptor variants, pigmentation, and skin cancer susceptibilityPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 6 2004Eugene Healy The melanocortin 1 receptor is a key regulator of variation in normal human pigmentation. Genetic variants of this receptor cause red hair and fair skin, and several case,control studies have demonstrated that these genetic variants increase the risk of skin cancer development in humans. The mechanism whereby the risks of skin cancer are increased is not entirely clear, and may be because of a combination of effects on pigmentation and non-pigmentary pathways. [source] The discovery of the human melanocytePIGMENT CELL & MELANOMA RESEARCH, Issue 3 2006Wiete Westerhof Summary Around 2200 bc the first written description of a human pigmentation disorder, most likely vitiligo, was recorded, and from that moment the history of research into human pigmentation can be traced. For the following 4000 yr, the origins of human skin colour remained an enigma that was to generate a multitude of misconceptions. Even after European physicians began to dissect and compare dark and light coloured skin to reveal its underlying anatomy, the origins of skin and hair pigmentation were a matter of frequently erroneous speculation. The true source of human pigmentation was only finally revealed with the discovery of the melanocyte in the 19th century. Once tyrosinase was identified to be the key enzyme in pigment formation, attention focused on elucidating the chemical structure of melanin, an enterprise that remains incomplete. The developmental origins of the melanocyte were described from 1940 to 1960, and the concept of the epidermal melanin unit was introduced together with a description of the ultrastructure of the melanosome and melanosome transfer. With these advances came the realization that different skin types exhibit distinct differences at the histological level that relate to varying amounts of eumelanin and pheomelanin produced by the melanocytes. The foundation established over the past 4000 yr is the basis for all current research into this fascinating cell type. [source] | |||||||||||||