C.R. Zhang

Sequencing-based approach identified three new susceptibility loci for psoriasis

In a previous large-scale exome sequencing analysis for psoriasis, we discovered seven common and low-frequency missense variants within six genes with genome-wide significance. Here we describe an in-depth analysis of noncoding variants based on sequencing data (10,727 cases and 10,582 controls) with replication in an independent cohort of Han Chinese individuals consisting of 4,480 cases and 6,521 controls to identify additional psoriasis susceptibility loci. We confirmed four known psoriasis susceptibility loci (IL12B, IFIH1, ERAP1 and RNF114; 2.30 × 10(-20)≤P≤2.41 × 10(-7)) and identified three new susceptibility loci: 4q24 (NFKB1) at rs1020760 (P=2.19 × 10(-8)), 12p13.3 (CD27-LAG3) at rs758739 (P=4.08 × 10(-8)) and 17q12 (IKZF3) at rs10852936 (P=1.96 × 10(-8)). Two suggestive loci, 3p21.31 and 17q25, are also identified with P<1.00 × 10(-6). The results of this study increase the number of confirmed psoriasis risk loci and provide novel insight into the pathogenesis of psoriasis.

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.

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.

Variation at HLA-DPB1 is associated with dermatomyositis in Chinese population.

Dermatomyositis (DM) is a polygenic disorder characterized by inflammation of skeletal muscle and skin. To date, the exact etiopathogenesis of DM remains elusive. To explore the genetic basis of DM, we conducted genome‐wide genotyping analysis of 127 patients and 1566 healthy controls by Illumina Human OmniZhongHua‐8 BeadChips in the Chinese Han population. We investigated whether the three SNP (rs7750458, rs9501251 and rs9500928) at 6p21.32 in the HLA‐DPB1 gene were significantly associated with DM (P < 5 × 10−8) and identified two susceptibility loci at 7q34 (PIP, rs9986765, P = 7.45 × 10−7, odds ratio [OR] = 2.71) and 10q24.2 (CPN1, rs3750716, P = 9.04 × 10−7, OR = 4.39) with suggestive evidence. We imputed 6674 classical human leukocyte antigen (HLA) alleles, amino acids and SNP from the discovery dataset, and stepwise analysis revealed that HLA‐DPB1*17 in class II HLA genes were significantly associated with DM susceptibility. This study represents the first genome‐wide association study (GWAS) of DM in the Chinese Han population. For the first time, HLA‐DPB1 was found to be associated with DM in this population. Moreover, we identified two novel suggestive susceptibility loci (PIP and CPN1) and confirmed four previously reported genes (DMB, DQA1, DQB1 and DRB1) having potential associations with DM in the Chinese Han population. Our GWAS results in this population should provide important information regarding the genetic etiopathogenesis of DM and facilitate the development of new therapies for the treatment of DM and the prevention of DM progression.

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.

PP-065 A clinical analysis of nosocomial fungal infection in same hospital for 4 years

glabrata 20/515 (3.88%), 21/828 (2.53%) and 20/825 (2.42%), Candida albicans 1/515 (0.19%), 03/828 (0.36%) and 05/825 (0.60%), Candida parapsilosis 01/515 (0.19%), 03/828 (0.36%) and 02/825 (0.24%) were isolated in samples taken and one isolate of Candida guillermondii in 2008 which is the first blood culture isolation of this Candida spp. in Sri Lanka. The most prevalent species was Candida tropicalis 19/41 (46.34%), 32/59 (54.23%) and 32/59 (54.23%) followed by Candida glabrata 20/41 (48.78%), 21/59 (35.59%) and 20/59 (33.89%) and Candida albicans 01/41 (2.43%), 03/59 (5.08%) and 05/59 (8.47%). Majority of isolates were sensitive to commonly used antifungal agents locally namely fluconazole and amphotericin B. Conclusion: The incidence is higher compared to the reported general incidence in Europe. The most prevalent species was Candida tropicalis which is the second most common spp in Europe. Candida albicans causing candidaemia in NCISL is extremely low though it was isolated in 35% of cases with haematological malignacies in Europe. Candida krusei has not been isolated at NCISL though it has been isolated in 12% of patients with haematological malignancies in Europe. Currently used antifungals can be continued for the management unless there is a special need for other antifungal agents for a special indication in a patient.