Five mutations of ATP2A2 gene in Chinese patients with Darier's disease and a literature review of 86 cases reported in China.

Darier's disease (DD) is an autosomal dominantly inherited skin disorder characterized by loss of adhesion between epidermal cells (acantholysis) and abnormal keratinization. To date, at least 140 mutations in the ATP2A2 gene have been identified as the genetic basis of DD. Here we reported three familial and two sporadic Chinese DD patients totally with four missense mutations (N767D, M494I, M494L, C318F) and one splice-site mutation (1288-6A-->G) in ATP2A2 gene, and presented a literature review of DD cases reported in China since 1989. Our data add new variants to the repertoire of ATP2A2 gene in DD and confirms that most mutations in the ATP2A2 gene are private and missense type. Likewise, the literature review indicates that DD is not uncommon in China and presents more information about genotype-phenotype correlations.

The association of the BLK gene with SLE was replicated in Chinese Han.

Systemic lupus erythematosus (SLE) is an autoimmune disease influenced by genetic and environmental factors. Recently, single nucleotide polymorphisms (SNPs) in the region of B lymphoid tyrosine kinase (BLK) have been shown to be associated with SLE in Caucasian population. In this paper, we genotyped SNP rs2248932 in 1,396 SLE patients of Chinese Han and 4,362 ethnically matched control subjects by using the Sequenom MassArray system. We confirmed that SNP rs2248932 in BLK gene was significantly associated with SLE (P = 1.41 x 10(-8) for the allele frequency, Odds ratio [OR] = 0.74, 95% confidence interval (CI): 0.66-0.82).The association of BLK in Chinese SLE patients was consistent with a dominant model (P = 8.88 x 10(-9), OR = 0.69, 95% CI: 0.61-0.79). In contrast to the Caucasian, this risk allele was the major allele in the Chinese Han; the risk allele frequency was higher in Chinese Han than in Caucasian. We did not find the association between this SNP and any subphenotype of SLE. The SNP rs2248932 was correlated to the expression of BLK mRNA. We conclude that the association of the BLK region with SLE was replicated in Chinese Han population living in mainland.

Genome-wide association study for vitiligo identifies susceptibility loci at 6q27 and the MHC.

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.

A novel KIT missense mutation in one Chinese family with piebaldism.

Piebaldism is an autosomal dominant disorder characterized by congenital leukoderma, mostly affecting forehead, abdomen and knee. Previous studies have revealed that piebaldism is caused by mutations of the KIT gene, which encodes the cell surface transmembrane tyrosine kinase receptor for KIT ligand. We reported here a Chinese Han family with piebaldism, and performed mutation detection of KIT gene by direct sequencing. A novel missense mutation C58G was identified in the patients, but not in the healthy individuals from the family and 100 unrelated controls. This study contributes to the database on KIT in piebaldism and enriches the knowledge about the genotype/phenotype correlation.

The analysis of genetics and associated autoimmune diseases in Chinese vitiligo patients.

Vitiligo is a common skin and hair depigmentary disorder that results from selective destruction of melanocytes. It occurs in a typical multifactorial, polygenic inheritance. Several studies have indicated that vitiligo is associated with some autoimmune diseases. In this paper we examined 6,516 vitiligo patients including clinical characteristics, familial involvement, and their association with other autoimmune diseases. Compared with sporadic vitiligo probands, familial vitiligo probands have earlier age onset and longer disease duration. The prevalences of four autoimmune diseases namely rheumatoid arthritis, chronic urticaria, alopecia areata and psoriasis, were significantly elevated in generalized vitiligo probands and their first-degree relatives. The prevalences of chronic urticaria, rheumatoid arthritis, psoriasis were much higher in familial generalized vitiligo probands. In addition, the prevalences of diabetes mellitus and asthma were also higher in familial vitiligo probands. These findings indicate that generalized vitiligo may share common genetic aetiologic links with other autoimmune diseases, and the genetic component of familial generalized vitiligo is stronger.

Prevalence and familial risk of ephelides in Han Chinese adolescents.

Ephelides are one of the most common lesions of skin pigmentation mainly on sun-exposed skin. Although they are benign pigmented spots, ephelides cause an increasing concern because of the wide-spreading cosmetic attention of society and possible association with skin cancer. However, there have been few reports on the prevalence of ephelides. The objective of this study was to estimate the prevalence of ephelides and the possible role of genetic factors in the pathogenesis of ephelides in the Han Chinese adolescents. Assessment of the skin was conducted in college students of the Anhui Medical University in China. Information on common skin conditions including ephelides were collected from 9697 Han Chinese college students. A total of 1,841 ephelides cases and 582 normal controls were identified and they, along with their first-degree relatives, provided information on ephelides conditions. The odds ratio was used to estimate the relative risk of ephelides between the first-degree relatives of cases and controls. The overall prevalence of ephelides was estimated to be 19.0% in college students. Ephelides are more common in female students (26.1%) than in males (12.1%; chi(2) = 06.7, P < 0.05). The mean ages of onset for males and females were 12.42 years (+/-4.61) and 12.88 years (+/-3.90; t = 2.11, P < 0.05), respectively. Positive family history was observed in 932 of the 1,841(50.6%) patients. The severity of ephelides in females of light skin was found to be significantly higher than that in males with skin of similar color (U = 3.904, P < 0.001). The risk of having ephelides among first-degree relatives of cases was significantly higher than that for the relatives of normal controls (odds ratio 5.75, 95% confidence interval (CI): 4.61-7.18, P < 0.001). Our study provided the first information on the prevalence of ephelides in Chinese adolescents and suggests that familial factors are important in determining individual susceptibility to ephelides.