Polymorphisms in the Melanocortin-1 Receptor (Mc1R) Gene in Vitiligo

Acar, Eylem; Bozkurt, Gökay; Görgülü, Adnan

doi:10.5152/balkanmedj.2011.007

Cited by 4 publications

(3 citation statements)

References 19 publications

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“…distribution of V60L shows that this allele is circumscribed to Europe and the Near East (Gerstenblith et al, 2007;Acar, Bozkurt and Görgülü, 2012;Galore-Haskel et al, 2009;Eskandani et al, 2010). However, we show that this increase in fitness for the population has collateral damaging consequences for the individual´s health.…”

Section: Discussionmentioning

confidence: 99%

Simultaneous Purifying Selection on the Ancestral MC1R Allele and Positive Selection on the Melanoma-Risk Allele V60L in South Europeans

Martínez-Cadenas¹,

López

Ribas

et al. 2013

Molecular Biology and Evolution

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In humans, the geographical apportionment of the coding diversity of the pigmentary locus melanocortin-1 receptor (MC1R) is, unusually, higher in Eurasians than in Africans. This atypical observation has been interpreted as the result of purifying selection due to functional constraint on MC1R in high UV-B radiation environments. By analyzing 3,142 human MC1R alleles from different regions of Spain in the context of additional haplotypic information from the 1000 Genomes (1000G) Project data, we show that purifying selection is also strong in southern Europe, but not so in northern Europe. Furthermore, we show that purifying and positive selection act simultaneously on MC1R. Thus, at least in Spain, regions at opposite ends of the incident UV-B radiation distribution show significantly different frequencies for the melanoma-risk allele V60L (a mutation also associated to red hair and fair skin and even blonde hair), with higher frequency of V60L at those regions of lower incident UV-B radiation. Besides, using the 1000G south European data, we show that the V60L haplogroup is also characterized by an extended haplotype homozygosity (EHH) pattern indicative of positive selection. We, thus, provide evidence for an adaptive value of human skin depigmentation in Europe and illustrate how an adaptive process can simultaneously help to maintain a disease-risk allele. In addition, our data support the hypothesis proposed by Jablonski and Chaplin (Human skin pigmentation as an adaptation to UVB radiation. Proc Natl Acad Sci U S A. 2010;107:8962-8968), which posits that habitation of middle latitudes involved the evolution of partially depigmented phenotypes that are still capable of suitable tanning.

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Section: Discussionmentioning

confidence: 99%

Simultaneous Purifying Selection on the Ancestral MC1R Allele and Positive Selection on the Melanoma-Risk Allele V60L in South Europeans

Martínez-Cadenas¹,

López

Ribas

et al. 2013

Molecular Biology and Evolution

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“…These negative correlations may represent a compensatory mechanism trying to correct the defective pigmentation. Some authors have reported that certain alleles of the MC1R gene might be protective against vitiligo, while others have found no significant relation between MC1R gene polymorphisms and vitiligo . On the other hand, a genome‐wide association analyses reported an association between the MC1R locus and generalised vitiligo …”

Section: Discussionmentioning

confidence: 99%

Assessment of gene expression levels of proopiomelanocortin (POMC) and melanocortin‐1 receptor (MC1R) in vitiligo

et al. 2015

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Proopiomelanocortin (POMC) and melanocortin 1 receptor (MC1R) are regulators of melanogenesis and pigmentation. Our objective was to estimate their levels, searching for a possible role of the melanocortin system in vitiligo. This study included 40 vitiligo patients and 40 controls. Skin biopsies were taken from lesional and non-lesional skin of patients and from the non-sun exposed skin of controls to detect the expression of POMC and MC1R using quantitative real-time polymerase chain reaction. Both factors were significantly lower in lesional than non-lesional skin and controls, while they were significantly higher in non-lesional skin than in controls. There was a statistically significant positive correlation between lesional levels of POMC and MC1R, as well as between non-lesional levels of POMC and MC1R in the patients. On the other hand, we found a statistically significant negative correlation between the lesional and non-lesional levels of POMC, as well as between the lesional and non-lesional levels of MC1R in the patients. As a conclusion, the melanocortin system could play a role in the pathogenesis of vitiligo or could be affected as the end result of the disease.

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“…Most vitiligo susceptibility loci encode melanocyte components, and antioxidant and immune-regulatory proteins [40,246]. For example, associations have been established between vitiligo pathogenesis and polymorphisms in tyrosinase (TYR) [247], catalase (CAT) [65], glutathione peroxidase (GPX) [65], melanocortin 1 receptor (MC1R) [248], major histocompatibility complex (MHC) [249], NACHT leucine-rich repeat protein 1 (NLRP1) [172] [252]. Both protective and susceptibility-increasing effects have been found in the case of different polymorphisms in these genes [253,254].…”

Section: Cross Talk Between Oxidative Stress Er Stress and Immune Symentioning

confidence: 99%

Could ER Stress Be A Major Link Between Oxidative Stress And Autoimmunity In Vitiligo?

Mansuri¹

2014

Pigmentary Disorders

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Polymorphisms in the Melanocortin-1 Receptor (Mc1R) Gene in Vitiligo

Cited by 4 publications

References 19 publications

Simultaneous Purifying Selection on the Ancestral MC1R Allele and Positive Selection on the Melanoma-Risk Allele V60L in South Europeans

Simultaneous Purifying Selection on the Ancestral MC1R Allele and Positive Selection on the Melanoma-Risk Allele V60L in South Europeans

Assessment of gene expression levels of proopiomelanocortin (POMC) and melanocortin‐1 receptor (MC1R) in vitiligo

Could ER Stress Be A Major Link Between Oxidative Stress And Autoimmunity In Vitiligo?

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