RESUMO
Vitiligo is an acquired pigmentary disorder characterized by loss of epidermal melanocytes. A strong association at a single nucleotide polymorphism (SNP) rs11966200 within MHC region had been identified in a recent genome-wide association study of generalized vitiligo in Chinese Han population. This study aims to investigate the relationships between SNP rs11966200 and the clinical features of generalized vitiligo in Chinese Han population. We compared the allele and genotype frequency among different vitiligo subphenotypes including age onset, extent of disease, clinical subtypes, family history of vitiligo and history of autoimmune disease. Our data showed SNP rs11966200 was associated with early-onset vitiligo (onset age ≤ 20 years) (odds ratio [OR], 1.54; p = 2.01 × 10(-13)), moderate-severe vitiligo (involved body surface ≥ 5 %) (OR, 1.17; p = 0.025), vitiligo vulgaris (OR, 1.13; p = 0.043), and focal vitiligo (OR, 0.86; p = 0.018). The study suggested that the underlying risk causal allele tagged by SNP rs11966200 might not only play important roles in the development of vitiligo, but also contribute to the diverse clinical characteristics of generalized vitiligo at least in Chinese Han population.
Assuntos
Povo Asiático/genética , Etnicidade/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Complexo Principal de Histocompatibilidade/genética , Polimorfismo de Nucleotídeo Único/genética , Vitiligo/genética , Adulto , Idade de Início , Alelos , Estudos de Casos e Controles , China , Feminino , Técnicas de Genotipagem , Humanos , Masculino , Fenótipo , Vitiligo/classificaçãoRESUMO
Psoriasis is a common inflammatory skin disease with genetic components of both immune system and the epidermis. PSOR1 locus (6q21) has been strongly associated with psoriasis; however, it is difficult to identify additional independent association due to strong linkage disequilibrium in the MHC region. We performed stepwise regression analyses of more than 3,000 SNPs in the MHC region genotyped using Human 610-Quad (Illumina) in 1,139 cases with psoriasis and 1,132 controls of Han Chinese population to search for additional independent association. With four regression models obtained, two SNPs rs9468925 in HLA-C/HLA-B and rs2858881 in HLA-DQA2 were repeatedly selected in all models, suggesting that multiple loci outside PSOR1 locus were associated with psoriasis. More importantly we find that rs9468925 in HLA-C/HLA-B is associated with both psoriasis and vitiligo, providing first important evidence that two major skin diseases share a common genetic locus in the MHC, and a basis for elucidating the molecular mechanism of skin disorders.
Assuntos
Antígenos HLA/genética , Polimorfismo de Nucleotídeo Único , Psoríase/genética , Vitiligo/genética , Adolescente , Adulto , Cromossomos Humanos Par 6/genética , Feminino , Predisposição Genética para Doença/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Antígenos HLA-DQ/genética , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Adulto JovemAssuntos
Psoríase/epidemiologia , Fumar/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , PrevalênciaRESUMO
Atopic dermatitis is a chronic, relapsing form of inflammatory skin disorder that is affected by genetic and environmental factors. We performed a genome-wide association study of atopic dermatitis in a Chinese Han population using 1,012 affected individuals (cases) and 1,362 controls followed by a replication study in an additional 3,624 cases and 12,197 controls of Chinese Han ethnicity, as well as 1,806 cases and 3,256 controls from Germany. We identified previously undescribed susceptibility loci at 5q22.1 (TMEM232 and SLC25A46, rs7701890, P(combined) = 3.15 × 10(-9), odds ratio (OR) = 1.24) and 20q13.33 (TNFRSF6B and ZGPAT, rs6010620, P(combined) = 3.0 × 10(-8), OR = 1.17) and replicated another previously reported locus at 1q21.3 (FLG, rs3126085, P(combined) = 5.90 × 10(-12), OR = 0.82) in the Chinese sample. The 20q13.33 locus also showed evidence for association in the German sample (rs6010620, P = 2.87 × 10(-5), OR = 1.25). Our study identifies new genetic susceptibility factors and suggests previously unidentified biological pathways in atopic dermatitis.
Assuntos
Povo Asiático/genética , Dermatite Atópica/genética , Loci Gênicos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Estudos de Casos e Controles , China/epidemiologia , Cromossomos Humanos Par 20/genética , Cromossomos Humanos Par 5/genética , Dermatite Atópica/epidemiologia , Proteínas Filagrinas , Humanos , Polimorfismo de Nucleotídeo Único/genética , Prognóstico , Fatores de RiscoRESUMO
A multicenter meta-analysis including data from 9,389 psoriasis patients and 9,477 control subjects was performed to investigate the contribution of the deletion of genes LCE3C and LCE3B, involved in skin barrier defense, to psoriasis susceptibility in different populations. The study confirms that the deletion of LCE3C and LCE3B is a common genetic factor for susceptibility to psoriasis in the European populations (OR(Overall) = 1.21 (1.15-1.27)), and for the first time directly demonstrates the deletion's association with psoriasis in the Chinese (OR = 1.27 (1.16-1.34)) and Mongolian (OR = 2.08 (1.44-2.99)) populations. The analysis of the HLA-Cw6 locus showed significant differences in the epistatic interaction with the LCE3C and LCE3B deletion in at least some European populations, indicating epistatic effects between these two major genetic contributors to psoriasis. The study highlights the value of examining genetic risk factors in multiple populations to identify genetic interactions, and indicates the need of further studies to understand the interaction of the skin barrier and the immune system in susceptibility to psoriasis.
Assuntos
Proteínas Ricas em Prolina do Estrato Córneo/genética , Deleção de Genes , Antígenos HLA-C/genética , Psoríase/genética , Adolescente , Adulto , Povo Asiático/genética , Epistasia Genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Fatores de Risco , População Branca/genética , Adulto JovemRESUMO
We conducted a genome-wide association study of generalized vitiligo in the Chinese Han population by genotyping 1,117 cases and 1,429 controls. The 34 most promising SNPs were carried forward for replication in samples from individuals of the Chinese Han (5,910 cases and 9,916 controls) and Chinese Uygur (713 cases and 824 controls) populations. We identified two independent association signals within the major histocompatibility complex (MHC) region (rs11966200, Pcombined=1.48x10(-48), OR=1.90; rs9468925, Pcombined=2.21x10(-33), OR=0.74). Further analyses suggested that the strong association at rs11966200 might reflect the reported association of the HLA-A*3001, HLA-B*1302, HLA-C*0602 and HLA-DRB1*0701 alleles and that the association at rs9468925 might represent a previously unknown HLA susceptibility allele. We also identified one previously undescribed risk locus at 6q27 (rs2236313, Pcombined=9.72x10(-17), OR=1.20), which contains three genes: RNASET2, FGFR1OP and CCR6. Our study provides new insights into the genetic basis of vitiligo.
Assuntos
Cromossomos Humanos Par 6/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Antígenos HLA/genética , Vitiligo/genética , Adolescente , Adulto , Idoso , Feminino , Frequência do Gene , Genótipo , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Antígenos HLA-DR/genética , Cadeias HLA-DRB1 , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Análise de Componente Principal , Adulto JovemRESUMO
Keloids are benign fibroproliferative dermal tumors of unknown etiology. Some studies have suggested that human HLA status might potentiate development of keloids phenotype. No report has been published about HLA class I alleles associated with keloids in Chinese Han individuals. To investigate the etiology of keloids, the polymerase chain reaction-sequence-specific primer (PCR-SSP) method was used to analyze the distribution of HLA class I alleles in 192 patients with keloids and 252 healthy controls in a Chinese Han population. The frequencies of HLA-A*03 (6.77% vs 0%, p(c) < 10(-7)), A*25 (10.16% vs 4.56%, p(c) = 0.0111), B*07 (7.81% vs 2.58%, p(c) = 0.0080), and Cw*0802 (19.79% vs 10.32%, p(c) = 0.0004) were significantly increased in keloid patients, whereas the frequency of HLA-A*01 (18.75% vs 38.10%, p(c) < 10(-7)) was highly decreased, compared with that in healthy controls. The A*03-B*07, A*25-B*07, A*03-Cw*0802, A*25-Cw*0802, and B*07-Cw*0802 were found as high-risk haplotypes in developing keloids in this study. No extended haplotype was found to be significantly related to keloids. Through stratified analysis, the association of subgroups (single site/multiple site, severity, and family history) of keloid patients with specific HLA alleles was identified. Our data suggest these alleles may be keloids susceptibility genes or may be in close linkage with the susceptibility genes.
Assuntos
Antígenos HLA/genética , Queloide/genética , Queloide/fisiopatologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , China , Análise Mutacional de DNA , Progressão da Doença , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Queloide/patologia , Masculino , Pessoa de Meia-Idade , Polimorfismo GenéticoRESUMO
BACKGROUND: The narrow host range of Mycobacterium leprae and the fact that it is refractory to growth in culture has limited research on and the biologic understanding of leprosy. Host genetic factors are thought to influence susceptibility to infection as well as disease progression. METHODS: We performed a two-stage genomewide association study by genotyping 706 patients and 1225 controls using the Human610-Quad BeadChip (Illumina). We then tested three independent replication sets for an association between the presence of leprosy and 93 single-nucleotide polymorphisms (SNPs) that were most strongly associated with the disease in the genomewide association study. Together, these replication sets comprised 3254 patients and 5955 controls. We also carried out tests of heterogeneity of the associations (or lack thereof) between these 93 SNPs and disease, stratified according to clinical subtype (multibacillary vs. paucibacillary). RESULTS: We observed a significant association (P<1.00x10(-10)) between SNPs in the genes CCDC122, C13orf31, NOD2, TNFSF15, HLA-DR, and RIPK2 and a trend toward an association (P=5.10x10(-5)) with a SNP in LRRK2. The associations between the SNPs in C13orf31, LRRK2, NOD2, and RIPK2 and multibacillary leprosy were stronger than the associations between these SNPs and paucibacillary leprosy. CONCLUSIONS: Variants of genes in the NOD2-mediated signaling pathway (which regulates the innate immune response) are associated with susceptibility to infection with M. leprae.
