Humans ; Hypopigmentation ; RNA, Long Noncoding/genetics* ; Vitiligo/genetics*

BABCKGROUND: Vitiligo is a cornmon disorder whose cause is not well understood. Up to 30% of patients had another family member with vitiligo which means that vitiligo is a heritable condition. We could not find any study for the genetics of vitiligo in Korean literature. OBJECTIVE: The purpose of this study was to clarify how genetic factors are involved in the pathogenesis of vitiligo in Korean patients. METHODS: We analyzed the 65 Korean vitiligo probands and their families. Each family was ascertained through a proband afflicted with vitiligo. RESULTS: 1. Focal type of vitiligo(44.6%) appeared to be with the highest frequency followed by the non-segmental generalized type(35.4%) and segmental type(20.0%). 2. The t,ype of vitiligo was not related with sex (p>0.9, X(2)(d.l=2) = 0.14). 3. There was a clear pattern of a familial aggregation of the vitiligo disease. In 29(44.6%) of these 65 proband families, at least one first-degree relative of the proband had vitiligo. The incidence of people affected among their 789 relatives (first, second and third-degree) was also found to be 9.13+/-1.03% 4. Several families in this study were shown to have father-son transmission of vitiligo, which indicates that vitiligo does not fit an x-linked inheritance. 5. There is a statistically significant departure frorn the expected which is inconsistent with a utosomal dominant inheritance (p<0.001, X(2)(d.l=2) = 52.32). 6. A single recessive model at the autosomal locus is not an explanation in deter mining the cause of vitiligo. The threshold trait among first-degree relatives(8.8%) shows a tendency to approach the square root of the frequency in the general population(10%) compared to those of dominant(50%) or recessive(25%) models. This result is consistent with a model of multifactorial inheritence for vitiligo. CONCLUSION: These result indicate that vitiligo is determined by a polygenic nature.
Genes, X-Linked ; Genetics* ; Humans ; Incidence ; Mining ; Vitiligo* ; Wills

OBJECTIVE: To explore the genetic basis for a patient with clinically suspected neurofibromatosis type I, alopecia areata and vitiligo. METHODS: Variant of the NF1 gene was detected by chip capture and high-throughput sequencing. Candidate variant was verified by Sanger sequencing of the family trio. RESULTS: The patient was found to harbor a novel missense c.1885G>A (p.Gly629Arg) variant of the NF1 gene, for which neither parent was carrier. The variant was not recorded in the public database. Based on the guidelines for genetic variation of the American College of Medical Genetics and Genomics, the c.1885G>A missense variant was predicted to be pathogenic (PS1+PS2+PM2+PP3+PP4). CONCLUSION The c.1885G>A missense variant probably underlay the disease in this child. Above finding has enriched the spectrum of the NF1 gene variants.
Alopecia Areata/genetics* ; Child ; Genomics ; Humans ; Mutation ; Neurofibromatosis 1/genetics* ; Vitiligo/genetics*

Among over 300 genodernatoses, causative genes have been identified in 170 monogenetic diseases, while gene mapping has been performed in over 100 monogenetic and polygenctic skin diseases. Researches in genodermatoses has rapidly advanced in China in recent ten years. The causative genes involved in multiple familial trichoepithelioma and primary erythermalgia have been found. Two independent genome-wide scans with DNA markers have been performed to detect genetic linkage related to psoriasis and vitiligo. In this review article, we summarize these most recent findings.
Erythromelalgia ; genetics ; HLA Antigens ; genetics ; Humans ; NAV1.7 Voltage-Gated Sodium Channel ; Proteins ; genetics ; Psoriasis ; genetics ; Sodium Channels ; genetics ; Vitiligo ; genetics

Adaptor Proteins, Signal Transducing ; genetics ; Adult ; Asian Continental Ancestry Group ; China ; ethnology ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Polymorphism, Single Nucleotide ; Vitiligo ; genetics

Variation in human skin and hair color is the most notable aspect of human variability and several studies in evolution, genetics and developmental biology contributed to explain the mechanisms underlying human skin pigmentation, which is responsible for differences in skin color across the world's populations. Despite skin pigmentation is primarily related to melanocytes functionality, the surrounding keratinocytes and extracellular matrix proteins and fibroblasts in the underlying dermal compartment actively contribute to cutaneous homeostasis. Many autocrine/paracrine secreted factors and cell adhesion mechanisms involving both epidermal and dermal constituents determine constitutive skin pigmentation and, whenever deregulated, the occurrence of pigmentary disorders. In particular, an increased expression of such mediators and their specific receptors frequently lead to hyperpigmentary conditions, such as in melasma and in solar lentigo, whereas a defect in their expression/release is related to hypopigmented disorders, as seen in vitiligo. All these interactions underline the relevant role of pigmentation on human evolution and biology.
Biology ; Cell Adhesion ; Developmental Biology ; Extracellular Matrix Proteins ; Fibroblasts ; Genetics ; Hair Color ; Homeostasis ; Humans ; Intercellular Signaling Peptides and Proteins ; Keratinocytes ; Lentigo ; Melanocytes ; Melanosis ; Pigmentation ; Skin Pigmentation* ; Skin* ; Vitiligo

OBJECTIVEGenetic factors are thought to be involved in the development of vitiligo. The aim of this study is to explore the possible genetic model of vitiligo by analyzing the genetic characteristics of 815 patients from Zhejiang province.

METHODSData for 815 patients with vitiligo together with their first- and second-degree relatives were obtained using a standardized questionnaire. All these information was requested to confirm the answers about family history in order to reduce the possibility of 'recall' bias. The 815 probands would include 411 (50.43%) males and 404 (49.57%) females with a varied age from 2 months to 71 years old. Since the information on general prevalence of vitiligo in this area was absent, a control group was set up to facilitate the calculations of heritability degree. 468 persons of the control group were from non-vitiligo population with a sex ratio of 241(male): 227(female) with varied age of 4 months to 80 years old. Both gender and age were comparable between the vitiligo and the control population. The inheritance pattern estimation, heritability calculation and complex segregation analysis were performed with Penrose method, Falconer regression method and SAGE-REGTL program.

RESULTSIn 815 vitiligo probands, 128 had and 687 had not family histories, with a heritability rate of 15.7%. The vitiligo prevalence in proband's first degree relatives was 2.580%, higher than the prevalence of 0.618% in second degree relatives, and both of them were higher than general prevalence: 0.192%. By Penrose method, the rates on different catagories were as follows: sibling prevalence rates s = 0.080 18; population prevalence rate q = 0.001 92; s/q = 41.76. The ratio of s/q did not approach 1/2q (260.42) or 1/4q (130.21), but approached 1/square root of q(22.82), suggesting vitiligo was consistent with a mode of polygenic inheritance. Using Falconer's method, heritabilities of vitiligo in first-and second degree relatives of probands were 59.61% (95% confidence interval 65.37-53.84) and 55.20% (95% confidence interval 43.88-66.52), respectively. The weighted average of heritability in all relatives was 58.7% (95% confidence interval 53.56-63.83). The results of complex segregation analysis suggested that major gene model including the Mendelian dominant, recessive and additive hypotheses were not rejected (P > 0.05). Purely environmental model and no transmission model were rejected at a 0. 001 significance level. According to AIC, Mendelian dominant inheritance was the best-fitted hypothesis.

CONCLUSIONGenetic factors played an important role in the occurrence of vitiligo, and the genetic model of vitiligo could serve as the polygenetic or multifactorial inheritance with major gene trait.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Humans ; Infant ; Male ; Middle Aged ; Models, Genetic ; Vitiligo ; epidemiology ; genetics ; Young Adult

OBJECTIVETo investigate the association of HLA class I and II alleles with generalized vitiligo in ethnic Han Chinese in north China.

METHODSBy employing polymerase chain reaction sequence-specific primer (PCR-SSP) procedure 34 generalized vitiligo patients in north China were studied for HLA I and II alleles and were compared with 102 healthy controls.

RESULTSThe allelic frequencies of HLA-A*30, Cw*06, DRB1*07, and DQB1*0201 were increased significantly in generalized vitiligo and especially in the patients without family history compared with the controls.

CONCLUSIONThese alleles positively associated with generalized vitiligo in Chinese Han patients in north China, might provide clues to reveal the susceptibility gene(s) of vitiligo in Chinese and as well as the immunnogenetic mechanisms of disease.

Adult ; Aged ; Aged, 80 and over ; Alleles ; Asian Continental Ancestry Group ; genetics ; China ; Female ; Gene Frequency ; Genes, MHC Class I ; genetics ; Genes, MHC Class II ; genetics ; Genotype ; Humans ; Male ; Middle Aged ; Vitiligo ; ethnology ; genetics

Genetic susceptibility is involved in the pathogenesis of vitiligo. Association studies with a whole genome-based approach instead of a single or a few candidate genes may be useful for discovering new susceptible genes. Although the etiology of non-segmental and segmental types is different, the association between gene polymorphisms and vitiligo has been reported, without defining types or in non-segmental type. Whole genome-based single nucleotide polymorphisms (SNPs) were examined in patients with non-segmental and segmental types of vitiligo using the Affymetrix GeneChip 500K mapping array, and 10 functional classes of significant SNPs were selected. Genotyping and data analysis of selected 10 SNPs was performed using real-time PCR. Genotype and allele frequencies were significantly different between both types of vitiligo and three of the target SNPs, DNAH5 (rs2277046), STRN3 (rs2273171), and KIAA1005 (rs3213758). A stronger association was suggested between the mutation in KIAA1005 (rs3213758) and the segmental type compared to the non-segmental type of vitiligo. DNAH5 (rs2277046), STRN3 (rs2273171), and KIAA1005 (rs3213758) may be new vitiligo-related SNPs in Korean patients, either non-segmental or segmental type.
Adaptor Proteins, Signal Transducing/*genetics ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group/*genetics ; Autoantigens/*genetics ; Axonemal Dyneins/*genetics ; Calmodulin-Binding Proteins/*genetics ; Child ; Child, Preschool ; Female ; Gene Frequency ; *Genome, Human ; Genome-Wide Association Study ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Republic of Korea ; Vitiligo/*genetics ; Young Adult

To compare the difference in tumor immunity and autoimmunity elicited by adenovirus (Ad) encoding human or murine tyrosinase-related protein 2 (AdhTRP2 or AdmTRP2), and to find the most effective way to induce immunity by AdhTRP2 or AdmTRP2, C57BL/6 mice were immunized with AdhTRP2 or AdmTRP2 intramuscularly at different doses of 10(5), 10(6), 10(7) and 10(8) separately (10 mice for each dose). Two weeks after the immunization, in vivo CTL assay and intracellular staining (ICS) of IFN-gamma were carried out to analyze the dose-effect relationship. Tumor growth and vitiligo (as an sign of autoimmunity) were observed until 3 months after challenge with 10(5) B16F10 tumor cells. The results showed that Ad encoding AdmTrp2 induced weak tumor immune response. Similar immunization with AdhTrp-2 elicited stronger protective immunity. CTL activity and IFN-gamma-produced CD8+T cells were directly proportional to dose of AdhTrp2 or AdmTrp2. Moreover, AdhTrp2 group showed tumor rejection in 100% of challenged mice till the end of 3rd month while 60% of mice immunized with AdmTrp2 were protected against tumor. In the whole process of this experiment, no vitiligo was observed in mice immunized either with AdhTrp2 or AdmTrp2. It is concluded that anti-melanoma responses induced by genetic vaccination expressing xenoantigens breaks immune tolerance effectively and is able to elicit strong antigen-specific cytotoxic T cell response without vitiligo.
Adenoviridae/metabolism ; Antineoplastic Agents/*pharmacology ; Cell Line, Tumor ; Cytokines/metabolism ; Immune System ; Immune Tolerance ; Interferon-gamma/metabolism ; Intramolecular Oxidoreductases/*biosynthesis ; Intramolecular Oxidoreductases/*genetics ; Mice, Inbred C57BL ; T-Lymphocytes, Cytotoxic/*metabolism ; Vitiligo/*metabolism