Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility.

Psoriasis is a common inflammatory skin disease with complex genetics and different degrees of prevalence across ethnic populations. Here we present the largest trans-ethnic genome-wide meta-analysis (GWMA) of psoriasis in 15,369 cases and 19,517 controls of Caucasian and Chinese ancestries. We identify four novel associations at LOC144817, COG6, RUNX1 and TP63, as well as three novel secondary associations within IFIH1 and IL12B. Fine-mapping analysis of MHC region demonstrates an important role for all three HLA class I genes and a complex and heterogeneous pattern of HLA associations between Caucasian and Chinese populations. Further, trans-ethnic comparison suggests population-specific effect or allelic heterogeneity for 11 loci. These population-specific effects contribute significantly to the ethnic diversity of psoriasis prevalence. This study not only provides novel biological insights into the involvement of immune and keratinocyte development mechanism, but also demonstrates a complex and heterogeneous genetic architecture of psoriasis susceptibility across ethnic populations.

Use of an Interferon-γ Release Assay in the Detection of Latent Tuberculosis in Dermatology: A Descriptive Analysis.

With the increasing use of biologic therapy in psoriasis, it is becoming more important to identify and treat latent tuberculosis (TB) infection (LTBI). Tuberculin skin test (TST) has been traditionally used to detect LTBI, but interferon-γ release assays (IGRAs), such as the T-SPOT.TB test (T-Spot), are increasingly being used in its place. The indications and results of 51 T-Spot tests performed at the National Skin Centre in Singapore between 2008 and 2010 were analyzed and compared with TST results, decision on LTBI treatment, and previous use of immunosuppressants. T-Spot was most commonly performed as part of a prebiologic workup in patients with psoriasis. A total of 14 (27.5%) results were positive, and no patients had features of active TB. Ten of these patients also underwent TST, five of whom had negative TST results. Six patients (11.8%) had equivocal results with T-Spot test. This study shows poor concordance between T-Spot test and TST. A high incidence of equivocal results in IGRA may limit the utility of the T-Spot test.

Association of skin barrier genes within the PSORS4 locus is enriched in Singaporean Chinese with early-onset psoriasis.

Psoriasis (OMIM#177900) is a common polygenic skin disorder affecting approximately 2% of the northern European population and 0.1% of the Han Chinese. Psoriasis patients suffer from chronic skin inflammation, manifested by erythematous scaly lesions. PSORS1-PSORS9 have been confirmed as psoriasis susceptibility loci in independent genetic studies on predominantly Caucasian populations, with psoriasis susceptibility loci (PSORS1, PSORS9) and additional loci at 9q33-34 and 2p22.3-11.2 reported in Han Chinese patients. In this study, we show the association of PSORS4 with psoriasis in Singaporean Chinese. Dense genotyping of single-nucleotide polymorphism-tagging candidate genes within the epidermal differentiation complex revealed significant association in the proximity of the involucrin gene (IVL); the strongest association was seen in early-onset psoriasis patients (P=0.0014). A follow-up genome-wide association screen localized the psoriasis susceptibility region to approximately 360 kb along chromosome 1 in the vicinity of IVL, small proline-rich region (SPRR) and proline-rich region 9 (PRR9) genes. The study of interactions between the causative variant(s) in this locus will provide insights into a possible role for epidermal barrier formation in the pathogenesis of psoriasis.

Spectrum of skin disorders in human immunodeficiency virus-infected patients in Singapore and the relationship to CD4 lymphocyte counts.

BACKGROUND: Skin disorders are extremely common and cause significant morbidity in human immunodeficiency virus (HIV)-infected individuals. There are few data on their prevalence and association with CD4 counts in Asians. AIM: To evaluate the prevalence of skin disorders in ambulatory HIV-infected individuals attending a specialized skin clinic in Singapore and the association with the degree of immunosuppression. METHODS: A cross-sectional study on skin disorders in HIV-positive outpatients in the Communicable Disease Centre of Singapore was performed. The association between skin disease prevalence and CD4 count was evaluated using logistic regression. RESULTS: Ninety-six patients (male : female, 8 : 1) were enrolled. The most common mode of HIV transmission was heterosexual (75%), followed by homosexual/bisexual contacts (22%), and intravenous drug abuse (3%). The distribution of patients in terms of current CD4 cell counts was as follows: 38.5% with less than 50 x 10(6)/L, 25% with between 50 and 199/microL, and 36.5% with at least 200 x 10(6)/L. The most common skin disorder was pruritic papular eruption (PPE) of HIV infection (31 cases), followed by psoriasis (24), seborrheic dermatitis (18), xerosis (17), herpes simplex (17), and adverse drug eruptions (17). A CD4 cell count of less than 200 x 10(6)/L was significantly associated with a higher number of skin disorders (P = 0.002) and the development of psoriasis [odds ratio (OR), 8.97; 95% confidence interval (CI), 1.70-47.16; P = 0.010], PPE (OR, 3.40; 95% CI, 1.21-9.53; P = 0.020), and adverse drug eruption (OR, 5.83; 95% CI, 1.21-28.00; P = 0.028). CONCLUSIONS: A preponderance of inflammatory dermatoses and an absence of skin tumors characterized this study. A low CD4 cell count was associated with a higher number of skin disorders and an increased incidence of PPE, psoriasis, and adverse drug eruptions.

Seroprevalence of herpes simplex virus-1 and -2 in attendees of a sexually transmitted infection clinic in Singapore.

BACKGROUND: We studied the seroprevalance of HSV (herpes simplex virus)-1 and HSV-2 in outpatient attendees of a sexually transmitted infection (STI) clinic in Singapore and examined their knowledge and attitudes towards HSV infection. METHODS: Two hundred male and 200 female participants were recruited in the study. Questionnaires were administered and blood samples were taken and analysed using the HerpeSelect 1 and 2 enzyme-linked immunosorbent assay (ELISA) IgG assays (type-specific serological tests). RESULTS: HSV-1 was positive in 223 (55.8%) individuals, negative in 175 (43.8%) and indeterminate in two (0.5%), whereas HSV-2 was positive in 114 (28.5%) individuals, negative in 284 (71.0%) and indeterminate in two (0.5%). The seroprevalance of HSV-2 was 26% and 31% in males and females, respectively. The correlation between a previous history of cold sores and HSV-1 infection was poor. On univariate analysis, there was a significant association with age, marital status and years of sex (P < 0.05) but after adjusting for confounders, none of the variables were significantly associated with HSV-2 seroprevalance. Most of the respondents (65.8%) were aware that herpes is an STI, whereas only half of them were aware of the possibility of asymptomatic transmission. CONCLUSION: Although HSV-2 is a common infection among STI clinic attendees in Singapore, there is an unsatisfactory level of knowledge among the attendees about HSV infection and public education programs should be introduced to address this.