Shengxiu Liu

Whole-exome SNP array identifies 15 new susceptibility loci for psoriasis

Genome-wide association studies (GWASs) have reproducibly associated ∼40 susceptibility loci with psoriasis. However, the missing heritability is evident and the contributions of coding variants have not yet been systematically evaluated. Here, we present a large-scale whole-exome array analysis for psoriasis consisting of 42,760 individuals. We discover 16 SNPs within 15 new genes/loci associated with psoriasis, including C1orf141, ZNF683, TMC6, AIM2, IL1RL1, CASR, SON, ZFYVE16, MTHFR, CCDC129, ZNF143, AP5B1, SYNE2, IFNGR2 and 3q26.2-q27 (P<5.00 × 10−08). In addition, we also replicate four known susceptibility loci TNIP1, NFKBIA, IL12B and LCE3D–LCE3E. These susceptibility variants identified in the current study collectively account for 1.9% of the psoriasis heritability. The variant within AIM2 is predicted to impact protein structure. Our findings increase the number of genetic risk factors for psoriasis and highlight new and plausible biological pathways in psoriasis.

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.

Condylomata gigantea in a male transsexual

Summary As the incidence of genital warts increases, warts arising in the mouth, throat and other sites can occasionally be seen. Condyloma gigantea in genital sites are often reported, but literature on genital warts in transsexuals is rare. We present a case of C. gigantea in a 23-year-old male-to-female transsexual, whose warts arose on the transplanted skin of a neovagina and in the perianal region. We conclude that although C. gigantea can occur in transsexuals, the best way to treat it is not clear.

Holmium laser treatment of genital warts: an observational study of 1500 cases.

The treatment and relapse rate of genital warts are significant problems. The aim of this observational study was to assess the efficacy of holmium laser treatment of genital warts. A total of 1500 outpatients with genital human papillomavirus-induced lesions presenting from August 2002 to June 2005 were treated with holmium laser. The effects and side-effects of treatment were observed and analysed. Of this large cohort, lesions were excised at the first visit in 1488 cases. Twelve cases were treated a second or third time in the event that the lesions were too large to be removed at the first visit. The incidence of side-effects and complications after treatment with holmium laser was found to be low. Almost all warts can be excised at first treatment by holmium laser therapy with little bleeding during the treatment.

Clinical efficacy of the 595 nm pulsed dye laser in the treatment of childhood superficial hemangioma - analysis of 10-year application in Chinese patients.

Abstract Background: The 595 nm tunable pulsed dye laser has been used in China for more than 10 years. However, no studies about its effect and side-effect in treatment of superficial hemangioma have been documented. Objective: This study was designed to retrospectively summarize its usage in Chinese patients. Methods: Infant patients with superficial hemangioma, who had received 595 nm tunable pulsed dye laser treatment in our laser center in the last 10 years, were recruited. Detailed demographics, results of assessment about their degree of clearance and clinical examination for treatment complications were entered into SASS10.0 version database, and statistical analyses were conducted. Results: Six hundred and fifty-seven cases with superficial hemangioma were recruited. The overall effectiveness rate was 91.17%. Female patients respond better than male, the difference was statistically significant (p < 0.001). Lesions at different part of the body respond differently to the treatment with lesions on extremities show the best result. The response rate does not increase with time of treatments. The most common side-effects were pigment changes and skin atrophy, which usually resolve spontaneously and disappear completely in a few months. Conclusions: Our experience confirmed the satisfactory clinical efficacy and safety of the 595 nm tunable pulse dye laser in the treatment of childhood superficial hemangioma.

Long-pulsed 1,064-nm high-energy dye laser improves resistant port wine stains: 20 report cases

Port wine stain (PWS) is one of the vascular birthmarks, which is commonly seen in the clinic. It is present at birth of the patients and grows commensurately [1]. The pulsed dynamic laser (PDL), which is based on selective photothermolysis, is now regarded as the first-line treatment for PWS [2]. The concept of selective photothermolysis with the 585and 595-nm PDL revolutionized the treatment of PWS, and most of PWS can be significantly lightened with the 595-nm PDL [3–5]. However, few PWS obtained complete recovery and nearly 20 to 30 % of them hardly lighten at all with PDL treatment [6]. In our cosmetic dermatology center, 595-nm PDL-resistant PWSwere documented since the last 6 years. In order to improve the treatment efficacy of the resistant PWS, we employed a new promising modality, long-pulsed yttrium– aluminum–garnet (YAG) 1,064-nm PDL, for the treatment of 595-nm PDL-resistant PWS. The aim of this study was to assess the role of the long-pulsed, 1,064-nm high-energy PDL in the treatment of resistant PWS.

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.

Treatment of facial recalcitrant verruca vulgaris with holmium: YAG laser: An update

Abstract Objectives: To evaluate the effect and safety of the holmium: YAG laser in the treatment of facial recalcitrant verruca vulgaris. Methods: 42 patients with recalcitrant facial verruca vulgaris (64 warts in all) were enrolled in the study. Warts were treated with holmium: YAG pulsed dye laser with a top energy of 1.2–1.5 J, pulse frequency 10–12 Hertz, average power 10 Watt. Adverse reaction, complication, recurrence and clinical assessment of the lesion were documented with follow-up 6 months. Results: Ages of patients ranged from 16 to 73 years. 62 warts in 42 patients were eliminated by only one treatment session. The average time for wound-healing is 10.3 days. No severe discomfort, bleeding, edema, ulceration and secondary infection developed. No obvious complications were found. Only 4 warts in 3 patients remained mild atrophy scar and 7 warts in 6 patients remained pigment change. These defects became slighter after 6-month follow-up and left no bad effect on aesthetic. Two of the patients encountered recurrence in the treated site follow-up 6 months. Conclusions: Holmium laser is an effective and safe therapy for recalcitrant verruca vulgaris. It is the choice of treatment for those lesions in cosmetically sensitive areas.

Topical application of 5-aminolevulinic acid followed by 595-nm pulsed dye laser irradiation for the treatment of recalcitrant port-wine stains: a primary study.

Abstract Objective: To evaluate the effectiveness and safety of topical application of 5-aminolevulinic acid (ALA) followed by pulsed dye laser (PDL) irradiation for the treatment of recalcitrant port-wine stain (PWS). Methods: Thirty-five patients (19 females and 16 males) with recalcitrant PWS were treated with topical application of 20% ALA and then irradiated with a 595-nm PDL (energy density of 6.5–9.0 J/cm2 and pulse duration of 6 or 10 ms) at 6–8 weeks intervals. Clinical improvement of lesions was evaluated by comparing photographs of lesions at baseline and 2 months after the last treatment. Results: Topical ALA spreading followed by irradiation with a 595-nm PDL improved PWS in 21 out of 35 patients who were previously recalcitrant to PDL treatment alone. Side effects were limited to transient erythema, vesicle formation, edema and mild purpura with no obvious subsequent scarring or undesirable pigment changes. Conclusion: The topical application of ALA followed by irradiation with a 595-nm PDL is an effective and safe treatment for PWS recalcitrant to PDL therapy alone.

Exome-wide association study identifies four novel loci for systemic lupus erythematosus in Han Chinese population

Objectives Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of considerable genetic predisposition. Genome-wide association studies have identified tens of common variants for SLE. However, the majority of them reside in non-coding sequences. The contributions of coding variants have not yet been systematically evaluated. Methods We performed a large-scale exome-wide study in 5004 SLE cases and 8179 healthy controls in a Han Chinese population using a custom exome array, and then genotyped 32 variants with suggestive evidence in an independent cohort of 13 246 samples. We further explored the regulatory effect of one novel non-coding single nucleotide polymorphism (SNP) in ex vivo experiments. Results We discovered four novel SLE gene regions (LCT, TPCN2, AHNAK2 and TNFRSF13B) encompassing three novel missense variants (XP_016859577.1:p.Asn1639Ser, XP_016859577.1:p.Val219Phe and XP_005267356.1:p.Thr4664Ala) and two non-coding variants (rs10750836 and rs4792801) with genome-wide significance (pmeta <5.00×10−8). These variants are enriched in several chromatin states of primary B cells. The novel intergenic variant rs10750836 exhibited an expression quantitative trait locus effect on the TPCN2 gene in immune cells. Clones containing this novel SNP exhibited gene promoter activity for TPCN2 (P=1.38×10−3) whose expression level was reduced significantly in patients with SLE (P<2.53×10−2) and was suggested to be further modulated by rs10750836 in CD19+ B cells (P=7.57×10−5) in ex vivo experiments. Conclusions This study identified three novel coding variants and four new susceptibility gene regions for SLE. The results provide insights into the biological mechanism of SLE.