X.-J. Zhang

Mechanisms of transforming growth factor β1/Smad signalling mediated by mitogen‐activated protein kinase pathways in keloid fibroblasts

Background  Keloids are recognized as benign tumours characterized by fibroblastic proliferation and accumulation of extracellular matrix, especially collagen deposition. The transforming growth factor (TGF)‐β1/Smad pathway plays an important role in keloid pathogenesis; however the underlying mechanisms are not fully understood.

Combined effects of HLA-Cw6 and cigarette smoking in psoriasis vulgaris: a hospital-based case-control study in China.

Background  Psoriasis is not only related to genetic factors but also to environmental factors. However, the combined effect of genetic and environmental factors in the development of psoriasis has still been unclear.

The effect of overweight and obesity on psoriasis patients in Chinese Han population: a hospital-based study.

Background  Accumulating evidence indicates that psoriasis is associated with increased risk of overweight and obesity. However, few studies have investigated this relationship in Chinese Han population.

Association between the PD1.3A/G polymorphism of the PDCD1 gene and systemic lupus erythematosus in European populations: a meta-analysis

Background  Linkage studies suggest a locus, SLEB2, involved in susceptibility to systemic lupus erythematosus (SLE) and programmed cell death 1 (PDCD1) gene locates in this region. The association of PDCD1 polymorphism (PD1.3A/G) with SLE has been widely investigated, but there are no unambiguous conclusions.

Comparisons of clinical features of HLA-DRB1*07 positive and negative vitiligo patients in Chinese Han population

Background  Human leucocyte antigen (HLA)‐II alleles have been found to be associated with vitiligo in different populations, and several studies also suggested that HLA class II alleles/haplotypes were associated with a different type vitiligo. Of HLA class II alleles, DRB1*07 has consistently shown a positive association with vitiligo in Chinese Han population.

Exome sequencing identifies SLC17A9 pathogenic gene in two Chinese pedigrees with disseminated superficial actinic porokeratosis

Background Disseminated superficial actinic porokeratosis (DSAP) is a rare autosomal dominant genodermatosis characterised by annular lesions that has an atrophic centre and a prominent peripheral ridge distributed on sun exposed area. It exhibits high heterogeneity, and five linkage loci have been reported. The mevalonate kinase (MVK) gene located on 12q24 has been confirmed as one of the disease-causing genes. But, the pathogenesis of a large part of DSAP remains unclear so far. Methods The recruited with DSAP carried no MVK coding mutations. Exome sequencing was performed in two affected and one unaffected individual in Family 1. Cosegregation of the candidate variants was tested in other family members. Sanger sequencing in 33 individuals with familial DSAP and 19 sporadic DSAP individuals was performed for validating the causative gene. Results An average of 1.35×105 variants were generated from exome data and 133 novel NS/SS/indels were identified as being shared by two affected individuals but absent in the unaffected individual. After functional prediction, 25 possible deleterious variants were identified. In Family 1, a missense variant c.932G>A (p.Arg311Gln) in exon 10 of SLC17A9 was observed in cosegregation with the phenotype; this amino acid substitution was located in a highly conserved major facilitator superfamily (MFS) domain in multiple mammalian. One additional missense variant c.25C>T (p.Arg9Cys) in exon 2 of SLC17A9 was found in Family 2. Conclusions The result identified SLC17A9 as another pathogenic gene for DSAP, which suggests a correlation between the aberrant vesicular nucleotide transporter and the pathogenesis of DSAP.

One novel and two recurrent mutations in the keratin 5 gene identified in Chinese patients with epidermolysis bullosa simplex

Epidermolysis bullosa simplex (EBS) is a group of inherited skin diseases, characterized by the formation of intraepidermal blisters. We performed genetic analysis of the keratin 5 (KRT5) gene in two Chinese pedigrees. One novel missense mutation was identified in a patient with sporadic EBS (general, non‐Dowling–Meara). Sequence analysis showed a heterozygous T > A transition at nucleotide 1730 of KRT5, changing phenylalanine (Phe) to tyrosine (Tyr) at position 577 of the keratin 5 (K5). In addition, two recurrent mutations c.1649delG (p.Gly550AlafsX77) and c.508G > (p.Glu170Lys) in KRT5 were identified in Chinese patients with mottled pigmentation EBS and localized EBS, respectively. None of the mutations were found in any unaffected family members or in an additional 100 unrelated control samples. These results suggest that these mutations are pathogenic and might be one of the potential causes of EBS in these Chinese patients.

Autoinhibition of IL-15 expression in KC cells is ERK1/2 and PI3K dependent

Interleukin (IL)‐15 is a proinflammatory cytokine and plays a key role in many diseases, including psoriasis. Although its signal transduction pathways in keratinocytes (KC) have been partially elucidated, the effects of IL‐15 on expression of IL‐15, IL‐6 and TNF‐α in KC are unknown. We have investigated the effects of IL‐15 on the expression of the three genes in primary culture of KC by the real‐time PCR, Western blot and ELISA. We observed that exogenous IL‐15 suppressed the endogenous expression of IL‐15, decreased the expression of IL‐6 at mRNA and protein levels in KC. The inhibition was blocked by anti‐IL‐15 monoclonal antibody and by inactive IL‐15, I50D mutant IL‐15. In contrast, IL‐15 increased TNF‐α transcription in these cells. Mechanistic studies demonstrated that the auto‐regulation of IL‐15 expression was dependent on activity of ERK1/2 and PI3K. Our studies suggest that there is an auto‐inhibitory mechanism controlling cellular IL‐15 levels.

A novel frameshift mutation of the EDA1 gene in a Chinese Han family with X‐linked hypohidrotic ectodermal dysplasia

Hypohidrotic ectodermal dysplasia (HED) is a rare skin disease characterized by hypotrichosis, hypodontia and hypohidrosis. HED can be autosomal dominant, autosomal recessive or X‐linked. However, X‐linked HED (XLHED; OMIM 305100) is the most common form. Mutations within the EDA1 gene, which encodes ectodysplasin‐A, are responsible for XLHED. In this study, we investigated the EDA1 gene in a Chinese Han family with XLHED, and found a novel 1‐bp deletion mutation (c.952delG) in exon 9 of the EDA1 gene, which results in a frameshift and premature termination codon. This result suggests that the c.952delG mutation of the EDA1 gene is likely to be the disease‐causing mutation for XLHED in this family. Our study adds new data to the worldwide knowledge of the molecular basis of XLHED.

A genetic coding variant rs72474224 in GJB2 is associated with clinical features of psoriasis vulgaris in a Chinese Han population

Our recent targeted sequencing study identified a missense single-nucleotide polymorphism rs72474224 (c.324C>T) in GJB2. To investigate the correlation between rs72474224 (c.324C>T) and subphenotypes of psoriasis, genotype data for rs72474224 (c.324C>T, p.Val37Ile) was analyzed in 9946 cases and 9906 controls. The additive model provided the best fit for rs72474224 (P = 7.34 × 10(-9)). The genotypic and allelic frequency distributions were associated with plaque psoriasis in case-only (Pgenotype = 2.67 × 10(-3), Pallele = 6.22 × 10(-4)) and subphenotype-control (Pgenotype = 1.58 × 10(-11), Pallele = 8.16 × 10(-12)) analyses. No other significant difference was found in case-only analyses. Rs72474224 in GJB2 is preferentially associated with plaque psoriasis in Chinese population and might contribute to the complexity of psoriasis clinical features.