RESUMO
Despite high prevalence, the etiopathology of melasma is not fully understood. Nevertheless, many factors have been associated with the disease, including: sun exposure, sex steroids hormones, drugs, stress, and pregnancy. The high occurrence within familiars (40-60%) suggests a genetic predisposition to the disease. This study explored, through complex segregation analysis (CSA), the inheritance model that best fit the family segregation pattern of facial melasma when accounting for the main epidemiological risk factors. We evaluated 686 subjects from 67 families, and 260 (38%) of them had facial melasma. The CSA model, adjusted for age, skin phototype, sex, sun exposure at work, hormonal oral contraceptive, and pregnancy, evidenced a genetic component that was best fitted to a dominant pattern of segregation. Melasma results from an interaction between exposure factors (e.g. pregnancy, hormones, and sun exposure) over genetically predisposed individuals.
Assuntos
Segregação de Cromossomos/genética , Genes Dominantes/genética , Predisposição Genética para Doença/genética , Melanose/epidemiologia , Melanose/genética , Adulto , Brasil/epidemiologia , Estudos de Casos e Controles , Face/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Pele/patologiaRESUMO
The Solute Carrier Family 45, Member 2 (SLC45A2) gene encodes the Membrane-Associated Transporter Protein (MATP), which mediates melanin synthesis by tyrosinase trafficking and proton transportation to melanosomes. At least two SLC45A2 coding SNPs [E272K (rs26722) and L374F (rs16891982)] were reported influencing normal variation of human pigmentation. Here we aimed at evaluating the influence of haplotypes of 12 SNPs within SLC45A2 in the determination of eye, hair and skin pigmentation in a highly admixed population sample and comparing their frequencies with the ones found in data retrieved from the 1000 Genomes Project. To achieve this goal, 12 SLC45A2 SNPs were evaluated in 288 unrelated individuals from the Ribeirão Preto city area, Southeastern Brazil. SNPs were genotyped by PCR-RFLP or Allele-specific PCR, followed by polyacrylamide gel electrophoresis. Haplotypes of each individual were inferred by two independent computational methods, PHASE and Partition-Ligation-Expectation-Maximization (PL-EM) algorithms, and 34 different haplotypes were identified. The hp9 haplotype was the most frequent (58.3%) and was associated with the presence of blond/red hair, pale skin, blue eyes and freckles. All haplotypes significantly associated with dark or light pigmentation features harbor the 374L and 374F alleles, respectively. These results emphasize the role played by haplotypes at SLC45A2 in the determination of pigmentation aspects of human populations and reinforce the relevance of SNP L374F in human pigmentation.
Assuntos
Cor de Olho/genética , Cor de Cabelo/genética , Haplótipos/genética , Melanose/genética , Pigmentação da Pele/genética , Alelos , Brasil , Frequência do Gene , Projeto Genoma Humano , Humanos , Polimorfismo de Fragmento de RestriçãoRESUMO
BACKGROUND: Melasma is a chronic acquired focal hypermelanosis affecting photoexposed areas, especially for women during fertile age. Several factors contribute to its development: sun exposure, sex steroids, medicines, and family history. Melanic pigmentation pathway discloses several SNPs in different populations. Here, we evaluated the association between genetic ancestry and facial melasma. METHODS: A cross-sectional study involving women with melasma and an age-matched control group from outpatients at FMB-Unesp, Botucatu-SP, Brazil was performed. DNA was extracted from oral mucosa swabs and ancestry determined by studying 61 INDELs. The genetic ancestry components were adjusted by other known risk factors by multiple logistic regression. RESULTS: We evaluated 119 women with facial melasma and 119 controls. Mean age was 39 ± 9 years. Mean age at beginning of disease was 27 ± 8 years. Pregnancy (40%), sun exposure (37%), and hormonal oral contraception (22%) were the most frequently reported melasma triggers. All subjects presented admixed ancestry, African and European genetic contributions were significantly different between cases and controls (respectively 10% vs 6%; 77% vs 82%; p < 0.05). African ancestry (OR = 1.04; 95% CI 1.01 to 1.07), first generation family history (OR = 3.04; 95% CI 1.56 to 5.94), low education level (OR = 4.04; 95% CI 1.56 to 5.94), and use of antidepressants by individuals with affected family members (OR = 6.15; 95% CI 1.13 to 33.37) were associated with melasma, independently of other known risk factors. CONCLUSIONS: Facial melasma was independently associated with African ancestry in a highly admixed population.
Assuntos
População Negra/genética , Melanose/genética , Adulto , Brasil , Estudos de Casos e Controles , Anticoncepcionais Orais/administração & dosagem , Anticoncepcionais Orais/efeitos adversos , Estudos Transversais , DNA/química , DNA/isolamento & purificação , DNA/metabolismo , Feminino , Humanos , Mutação INDEL , Modelos Logísticos , Melanose/etiologia , Pessoa de Meia-Idade , Mucosa Bucal/metabolismo , Razão de Chances , Gravidez , Fatores de Risco , População Branca/genéticaRESUMO
The pathogenesis of melasma, a common, photo-induced hyperpigmentary disorder, is not clearly understood. Significant factors linked to melasma are ultraviolet radiation exposure and genetic predisposition. Histological analysis has demonstrated that melasma is caused by a network of cellular interactions among melanocytes, keratinocytes, mast cells, fibroblasts, and dermal vasculature exhibits, features similar to chronic sun damage. Dermal inflammation caused by ultraviolet radiation might play an important role in the hyperpigmentation and reactivation of melasma lesions through the production of melanogenic cytokines and growth factors. Because the role of inflammation in this disorder is unknown, we used histochemistry, immunohistochemistry, and quantitative real-time polymerase chain reaction to evaluate melasma lesions from healthy female patients (n = 20) with malar melasma. Lesional skin without specific solar exposure or photoprotection measures within the previous 4 weeks was compared with nonlesional skin. The increased lymphocytic infiltrate in lesional skin was mainly composed of CD4 T cells, mast cells, and macrophages. Levels of the cytokine interleukin (IL)-17 and the proinflammatory mediator cyclooxygenase (COX)-2 were significantly elevated in affected skin compared with healthy skin. In addition, the Melasma Activity and Severity Index score, fraction of solar elastosis, and epidermal melanin were positively associated with COX-2 expression. There was no statistically significant difference in IL-1α, IL-1ß, R-IL1, IL-6, IL-8, vascular endothelial growth factor, and tumor necrosis factor alpha expression levels. Together, these data indicated that melasma under unchallenged conditions is characterized by chronic inflammatory cells and mediators, which may explain its recurrent nature.
Assuntos
Antígenos CD4/análise , Ciclo-Oxigenase 2/análise , Dermatite/imunologia , Mediadores da Inflamação/análise , Interleucina-17/análise , Melanose/imunologia , Pele/imunologia , Imunidade Adaptativa , Adulto , Doenças Assintomáticas , Biomarcadores/análise , Estudos de Casos e Controles , Ciclo-Oxigenase 2/genética , Dermatite/enzimologia , Dermatite/genética , Dermatite/patologia , Feminino , Humanos , Imunidade Inata , Imuno-Histoquímica , Interleucina-17/genética , Melanose/enzimologia , Melanose/genética , Melanose/patologia , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Pele/enzimologia , Pele/patologia , Regulação para CimaRESUMO
The Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD), located in Manaus, the capital of the State of Amazonas (Western Brazilian Amazon), is a pioneering institution in this region regarding the syndromic surveillance of acute febrile illness, including arboviral infections. Based on the data from patients at the FMT-HVD, we have detected recurrent outbreaks in Manaus by the four dengue serotypes in the past 15 years, with increasing severity of the disease. This endemicity has culminated in the simultaneous circulation of all four serotypes in 2011, the first time this has been reported in Brazil. Between 1996 and 2009, 42 cases of yellow fever (YF) were registered in the State of Amazonas, and 71.4% (30/42) were fatal. Since 2010, no cases have been reported. Because the introduction of the yellow fever virus into a large city such as Manaus, which is widely infested by Aedes mosquitoes, may pose a real risk of a yellow fever outbreak, efforts to maintain an appropriate immunization policy for the populace are critical. Manaus has also suffered silent outbreaks of Mayaro and Oropouche fevers lately, most of which were misdiagnosed as dengue fever. The tropical conditions of the State of Amazonas favor the existence of other arboviruses capable of producing human disease. Under this real threat, represented by at least 4 arboviruses producing human infections in Manaus and in other neighboring countries, it is important to develop an efficient public health surveillance strategy, including laboratories that are able to make proper diagnoses of arboviruses.
Assuntos
Animais , Melanose/genética , Pigmentação/genética , Receptor Tipo 1 de Melanocortina/genética , Sciuridae/genética , Sequência de Aminoácidos , Evolução Molecular , Estudos de Associação Genética , Variação Genética , Dados de Sequência Molecular , Linhagem , Sciuridae/classificação , Deleção de Sequência/genéticaRESUMO
Morphological variation in natural populations is a genomic test bed for studying the interface between molecular evolution and population genetics, but some of the most interesting questions involve non-model organisms that lack well annotated reference genomes. Many felid species exhibit polymorphism for melanism but the relative roles played by genetic drift, natural selection, and interspecies hybridization remain uncertain. We identify mutations of Agouti signaling protein (ASIP) or the Melanocortin 1 receptor (MC1R) as independent causes of melanism in three closely related South American species: the pampas cat (Leopardus colocolo), the kodkod (Leopardus guigna), and Geoffroy's cat (Leopardus geoffroyi). To assess population level variation in the regions surrounding the causative mutations we apply genomic resources from the domestic cat to carry out clone-based capture and targeted resequencing of 299 kb and 251 kb segments that contain ASIP and MC1R, respectively, from 54 individuals (13-21 per species), achieving enrichment of ~500-2500-fold and ~150x coverage. Our analysis points to unique evolutionary histories for each of the three species, with a strong selective sweep in the pampas cat, a distinctive but short melanism-specific haplotype in the Geoffroy's cat, and reduced nucleotide diversity for both ancestral and melanism-bearing chromosomes in the kodkod. These results reveal an important role for natural selection in a trait of longstanding interest to ecologists, geneticists, and the lay community, and provide a platform for comparative studies of morphological variation in other natural populations.
Assuntos
Proteína Agouti Sinalizadora/genética , Evolução Molecular , Melanose/genética , Receptor Tipo 1 de Melanocortina/genética , Seleção Genética/genética , Animais , Gatos , Variação Genética , Genética Populacional , Haplótipos , Mutação , Filogenia , América do Sul , Especificidade da EspécieRESUMO
Gastrointestinal stromal tumors (GIST) are the most common mesenchymatous neoplasms of the human digestive tract. They locate preferentially in stomach, duodenum or small bowel. Usually sporadic, familial cases unrelated to neurofibromatosis may be due to germline mutations in KIT or PDGFRA. We describe the first Argentine family with GIST in which we found, diffuse cutaneous melanosis, lentiginosis, and dysphagia. Dysphagia was not observed in the four families previously described with the same mutation. Histopathology resulted consistent with GIST, and tumor immunohistochemistry was likewise positive for DOG-1, CD117 (KIT) and CD34. The search for germline mutations identified the KIT c.1697T > C (p.559V > A) substitution in exon 11. Treatment with imatinib is furnishing positive results.
Assuntos
Transtornos de Deglutição/genética , Tumores do Estroma Gastrointestinal/genética , Mutação em Linhagem Germinativa/genética , Melanose/genética , Proteínas Proto-Oncogênicas c-kit/genética , Adolescente , Adulto , Criança , Transtornos de Deglutição/diagnóstico , Feminino , Tumores do Estroma Gastrointestinal/diagnóstico , Humanos , Imuno-Histoquímica , Masculino , Melanose/diagnóstico , Pessoa de Meia-Idade , LinhagemRESUMO
BACKGROUND: Melasma is an acquired, irregularly patterned, light to dark-brown hypermelanosis, with symmetric distribution mostly over the face. The aim of this study was to evaluate clinical characteristics and factors related to melasma in Brazilian patients. METHODS: This was a cross-sectional, multicenter study performed in Brazil. Investigators examined and questioned 953 patients over 18 years of age on clinical characteristics and other factors related to their melasma. RESULTS: Melasma was more prevalent in women (97.5%) and in Fitzpatrick skin phototypes II (12.8%), III (36.3%), and IV (39.7%). Skin phototypes II and III and family history of melasma had early onset of the disorder when compared with skin phototypes IV, V, and VI (P<0.0001). Similar results were also observed when these same groups were compared with the absence of family history (P<0.0001). Extra-facial melasma was more frequent in postmenopausal women compared with those who were not experiencing menopause (14.2% vs. 3.5%, P<0.0001). CONCLUSIONS: Data suggested that the age of melasma onset are related to skin phototypes and family history. Additionally, extra-facial melasma was more common in menopausal women. This is the first study on the epidemiology of melasma in Brazil involving a large sample of the population. These data can be a source of new relevant research on the cause and development of melasma.
Assuntos
Idade de Início , Melanose/epidemiologia , Complicações na Gravidez/epidemiologia , Pigmentação da Pele , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Estudos Transversais , Face , Feminino , Humanos , Masculino , Melanose/etiologia , Melanose/genética , Pessoa de Meia-Idade , Pós-Menopausa , Gravidez , Prevalência , Fatores Sexuais , Inquéritos e Questionários , Raios Ultravioleta/efeitos adversos , Adulto JovemRESUMO
Gastrointestinal stromal tumors (GIST) are the most common mesenchymatous neoplasms of the human digestive tract. They locate preferentially in stomach, duodenum or small bowel. Usually sporadic, familial cases unrelated to neurofibromatosis may be due to germline mutations in KIT or PDGFRA. We describe the first Argentine family with GIST in which we found, diffuse cutaneous melanosis, lentiginosis, and dysphagia. Dysphagia was not observed in the four families previously described with the same mutation. Histopathology resulted consistent with GIST, and tumor immunohistochemistry was likewise positive for DOG-1, CD117 (KIT) and CD34. The search for germline mutations identified the KIT c.1697T > C (p.559V > A) substitution in exon 11. Treatment with imatinib is furnishing positive results.
Assuntos
Transtornos de Deglutição/genética , Tumores do Estroma Gastrointestinal/genética , Mutação em Linhagem Germinativa/genética , Melanose/genética , Proteínas Proto-Oncogênicas c-kit/genética , Adolescente , Adulto , Criança , Transtornos de Deglutição/diagnóstico , Feminino , Tumores do Estroma Gastrointestinal/diagnóstico , Humanos , Imuno-Histoquímica , Masculino , Melanose/diagnóstico , Pessoa de Meia-Idade , LinhagemRESUMO
Gastrointestinal stromal tumors (GIST) are the most common mesenchymatous neoplasms of the human digestive tract. They locate preferentially in stomach, duodenum or small bowel. Usually sporadic, familial cases unrelated to neurofibromatosis may be due to germline mutations in KIT or PDGFRA. We describe the first Argentine family with GIST in which we found, diffuse cutaneous melanosis, lentiginosis, and dysphagia. Dysphagia was not observed in the four families previously described with the same mutation. Histopathology resulted consistent with GIST, and tumor immunohistochemistry was likewise positive for DOG-1, CD117 (KIT) and CD34. The search for germline mutations identified the KIT c.1697T > C (p.559V > A) substitution in exon 11. Treatment with imatinib is furnishing positive results.
Assuntos
Melanose/genética , Mutação em Linhagem Germinativa/genética , Proteínas Proto-Oncogênicas c-kit/genética , Transtornos de Deglutição/genética , Tumores do Estroma Gastrointestinal/genética , Adolescente , Adulto , Criança , Feminino , Humanos , Imuno-Histoquímica , Linhagem , Masculino , Melanose/diagnóstico , Pessoa de Meia-Idade , Transtornos de Deglutição/diagnóstico , Tumores do Estroma Gastrointestinal/diagnósticoRESUMO
Los mosaicismos pigmentarios son enfermedades névicas caracterizadas por la presencia en piel de máculas híper o hipopigmentadas de distribución según patrones clínicos preestablecidos. En ocasiones presentan asociaciones extracutáneas que alteran el desarrollo normal del individuo. Presentamos una recopilación de todos los casos de mosaicismos pigmentarios evaluados en nuestro Servicio en laúltima década
Assuntos
Humanos , Masculino , Feminino , Melanose/genética , Melanose/patologia , Hiperpigmentação/genética , Hiperpigmentação/patologia , Hipopigmentação/genética , Hipopigmentação/patologia , Mosaicismo , Pele/patologia , Cromossomo XRESUMO
Among the various types of pigmentary disturbances associated with mosaicism, the phylloid pattern (Greek phyllon = leaf, eidos = form) is characterized by multiple leaf-like patches reminiscent of an art nouveau painting. The number of cases displaying this unusual pattern is so far limited. We describe a phylloid pattern of hypomelanosis in a 3-year-old girl with multiple congenital anomalies including microcephaly, midfacial hypoplasia, cleft lip, coloboma, posteriorly rotated ears, pectus carinatum, and pronounced mental and physical retardation. In addition, this child had oval or oblong patches of hyperpigmentation involving the trunk in a horizontal arrangement dissimilar from the phylloid hypomelanotic pattern. In peripheral blood lymphocytes a karyotype 46,XX,-13,+t(13q;13q) was consistently found, whereas cultured skin fibroblasts showed a complex form of mosaicism comprising three different abnormal cell lines (46,XX,-13,+t(13q;13q)/45,XX,-13/45,XX,-13,+frag). This case provides further evidence that the phylloid pattern represents a separate category of pigmentary disturbance to be distinguished from other types of cutaneous mosaicism such as the lines of Blaschko or the checkerboard arrangement.
Assuntos
Anormalidades Múltiplas/genética , Cromossomos Humanos Par 13 , Hipopigmentação/genética , Melaninas/deficiência , Melanose/genética , Mosaicismo/genética , Adulto , Pré-Escolar , Citogenética , Feminino , Humanos , Hipopigmentação/patologia , Pele/patologia , Cromossomo XRESUMO
Se reporta un caso de lactante mayor femenino de 2 meses de edad, portador de lesiones cutáneas hipocrómicas, congénitas, con alteración del desarrollo musculoesquelético y alteraciones neurológicas leves. El hallazgo histopatológico de las lesiones cutáneas fue compatible con Hipomelanosis de Ito. El cariotipo de fibroblastos de piel y de linfocitos de sangre periférica se reportó como 46, XX normal. Se revisa en la literatura los reportes de alteraciones extracutáneas asociadas y criterios diagnósticos
Assuntos
Humanos , Feminino , Lactente , Doenças Ósseas Metabólicas/patologia , Fibroblastos/classificação , Incontinência Pigmentar , Melanose/diagnóstico , Melanose/genética , Neurofibromatoses/genética , Pele/lesõesRESUMO
Melasma is characterized by a facial hypermelanosis of light to dark brown color, being more common in women of Hispanic origin. In this study, 27 men with melasma were evaluated clinically and histologically to compare their features with those of previous studies. Three patterns of localization were recognized, namely, centrofacial, malar, and mandibular. On the basis of Wood's light examination, an epidermal, a dermal, and a mixed type were identified. Epidermal hyperpigmentation only and epidermal and dermal hyperpigmentation were found in histologic analysis of the cases. Significant etiologic factors included exposure to sunlight in 66.6% as well as a familial predisposition in 70.4% of the cases. This study demonstrated that melasma in men shares the same clinicohistologic characteristics as in women, but hormonal factors do not seem to play major significant role.