<scp>MC</scp>1R, the c<scp>AMP</scp> pathway, and the response to solar <scp>UV</scp>: extending the horizon beyond pigmentation

García‐Borrón, José C.; Abdel‐Malek, Zalfa; Jiménez‐Cervantes, Celia

doi:10.1111/pcmr.12257

Cited by 160 publications

(165 citation statements)

References 250 publications

(396 reference statements)

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“…Population-based studies in diverse ethnic groups have shown the MC1R gene to be highly polymorphic with around 200 allelic variants identified [26,27] , 9 common variants are recognised in populations with European ancestry [28] . In Caucasians, some of the MC1R variants known as R -alleles, with a combined frequency of 18%, have a strong association with red hair, fair skin, freckling as well as increased melanoma and non-melanoma skin cancer risk.…”

Section: Mc1r: α-Msh Receptor and The Gene For Red Hair Colourmentioning

confidence: 99%

“…In Caucasians, some of the MC1R variants known as R -alleles, with a combined frequency of 18%, have a strong association with red hair, fair skin, freckling as well as increased melanoma and non-melanoma skin cancer risk. The most common R variant alleles are D84E, R142H, R151C, R160W and D294H [26,29] . MC1R alleles less penetrant for RHC are known as r -alleles of 27%, with the normal wild type allele (WT) at around 50% frequency.…”

Section: Mc1r: α-Msh Receptor and The Gene For Red Hair Colourmentioning

confidence: 99%

“…It is now recognized that MC1R has effects that extend beyond pigmentation, and involve the activation of the DNA damage response in human melanocytes. This role of MC1R is pivotal for the prevention of photo-carcinogenesis; it displays MC1R function as a melanoma predisposition gene and reveals how the expression of RHC variants increases melanoma risk [26,27] .…”

Section: Mc1r: α-Msh Receptor and The Gene For Red Hair Colourmentioning

confidence: 99%

“…Conversely, low tyrosinase activity and high availability of cysteine lead to the less photoprotective and potentially phototoxic pheomelanins [31] . The main determinant of the amount and type of pigments formed within epidermal melanocytes is the MC1R genotype status [26,28] .…”

Section: Mc1r: α-Msh Receptor and The Gene For Red Hair Colourmentioning

confidence: 99%

“…Protein kinase A (PKA) is then activated, followed by the phosphorylation of members of the cAMP responsive-element binding protein (CREB) family of transcription factors, and CREB-mediated activation of Microphthalmia transcription factor ( MITF ) gene expression. MITF is a key positive regulator of melanocyte differentiation markers including tyrosinase activity, increased protein levels of TYRP1 and dopachrome tautomerase (DCT), leading to the biosynthesis of eumelanin pigments [26,28] .…”

Section: Mc1r: α-Msh Receptor and The Gene For Red Hair Colourmentioning

confidence: 99%

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Skin Pigmentation Genetics for the Clinic

Ainger

Jagirdar²,

Lee³

et al. 2017

Dermatology

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Human pigmentation characteristics play an important role in the effects of sun exposure, skin cancer induction and disease outcomes. Several of the genes most important for this diversity are involved in the regulation and distribution of melanin pigmentation or enzymes involved in melanogenesis itself within the melanocyte cell present in the skin, hair and eyes. The single nucleotide polymorphisms and extended haplotypes within or surrounding these genes have been identified as risk factors for skin cancer, in particular, melanoma. These same polymorphisms have been under selective pressure leading towards lighter pigmentation in Europeans in the last 5,000-20,000 years that have driven the increase in frequency in modern populations. Although pigmentation is a polygenic trait, due to interactive and quantitative gene effects, strong phenotypic associations are readily apparent for these major genes. However, predictive value and utility are increased when considering gene polymorphism interactions. In melanoma, an increased penetrance is found in cases when pigmentation gene risk alleles such as MC1R variants are coincident with mutation of higher-risk melanoma genes including CDKN2A, CDK4 and MITF E318K, demonstrating an interface between the pathways for pigmentation, naevogenesis and melanoma. The clinical phenotypes associated with germline changes in pigmentation and naevogenic genes must be understood by clinicians, and will be of increasing relevance to dermatologists, as genomics is incorporated into the delivery of personalised medicine.

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Section: Mc1r: α-Msh Receptor and The Gene For Red Hair Colourmentioning

confidence: 99%

Section: Mc1r: α-Msh Receptor and The Gene For Red Hair Colourmentioning

confidence: 99%

Section: Mc1r: α-Msh Receptor and The Gene For Red Hair Colourmentioning

confidence: 99%

Section: Mc1r: α-Msh Receptor and The Gene For Red Hair Colourmentioning

confidence: 99%

Section: Mc1r: α-Msh Receptor and The Gene For Red Hair Colourmentioning

confidence: 99%

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Skin Pigmentation Genetics for the Clinic

Ainger

Jagirdar²,

Lee³

et al. 2017

Dermatology

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The MC1R melanoma risk variant p.R160W is associated with Parkinson disease

Tell‐Martí

Puig-Butillé

Potrony

et al. 2015

Annals of Neurology

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Epidemiological studies have reported the co-occurrence of Parkinson disease (PD) and melanoma. Common genetic variants in the MC1R (melanocortin 1 receptor) gene, which determines skin and hair color, are associated with melanoma. Here we investigated whether genetic variants in MC1R modulate the risk of PD by sequencing the entire gene in 870 PD patients and 736 controls ascertained from Spain. We found that the MC1R variant p.R160W (rs1805008) is marginally associated with PD (odds ratio = 2.10, gender- and age-adjusted p = 0.009, Bonferroni-corrected p = 0.063). Our results suggest that MC1R genetic variants modulate the risk of PD disease in the Spanish population.

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Systematic analysis of genetic variants in patients with essential tremor

et al. 2018

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BackgroundEssential tremor (ET), a prevalent neurological disorder, is featured by postural and kinetic tremors in upper limbs. Studies of twins and families indicate an important role for genetic factors in ET development. There are substantial overlaps between ET and Parkinson's disease (PD). The aim of this study was to examine the possible roles of genetic variants in ET development.MethodsA total of 200 Han Chinese ET patients and 432 ethnically matched normal controls were enrolled, and genetic analysis of 23 variants in 15 genes was performed.ResultsGenotypic and allelic frequencies of the melanocortin 1 receptor gene (MC1R) variant rs34090186 showed statistically significant differences in ET patients and controls (p = 0.027 and 0.028, odds ratio = 2.789 and 2.744, 95% confidence interval: 1.084–7.179 and 1.075–7.005). No statistically significant difference was revealed in either genotypic or allelic distributions of other variants or haplotypes (all p > 0.05).ConclusionsThe discrepancies found in this study indicate the variant rs34090186 in the MC1R gene, some variants of which were reported to be related to increased risk of PD and melanoma, may play a risk role in ET, confirming a potential association between ET and PD. Evidence supporting ET‐PD link will continue to accumulate and improve our understanding of any underlying mechanisms for both disorders.

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MC1R, the cAMP pathway, and the response to solar UV: extending the horizon beyond pigmentation

Cited by 160 publications

References 250 publications

Skin Pigmentation Genetics for the Clinic

Skin Pigmentation Genetics for the Clinic

The MC1R melanoma risk variant p.R160W is associated with Parkinson disease

Systematic analysis of genetic variants in patients with essential tremor

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