Gene-gene interactions in IL23/Th17 pathway contribute to psoriasis susceptibility in Chinese Han population.

BACKGROUND: Psoriasis is a common chronic inflammatory skin disease. IL23/Th17 is a newly confirmed pathway in psoriasis. OBJECTIVE: To investigate the gene-gene interactions in IL23/Th17 pathway underlying psoriasis. METHODS: A total of 299 single-nucleotide polymorphisms from 11 genes in IL23/Th17 pathway were genotyped on 1139 patients with psoriasis and 1694 controls. Multifactor dimensionality reduction and logistic regression algorithms were applied to explore the gene-gene interactions. RESULTS: We found that there were a three-way interaction among IL21, CCR4 and TNF(χ(2) = 5.02(1), P = 0.025) and three pair-wise gene-gene interactions between IL12RB1 and CCR4(χ(2) = 11.66(4), P = 0.0201), IL22 and CCR4 (χ(2) = 11.97(4), P = 0.0176), IL12RB1 and IL6 (χ(2) = 7.31(1), P = 0.0069) in psoriasis. CONCLUSIONS: Our results might be helpful for explaining the missing heritability of the psoriasis due to epistasis and provide a deep insight into the important role of the IL23/Th17 pathway in the pathogenesis of psoriasis.

Genetic variant rs4982958 at 14q11.2 is associated with allergic rhinitis in a Chinese Han population running title: 14q11.2 is a susceptibility locus for allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is one of the most common diseases caused by the combined effects of intrinsic factors (susceptibility genes and immunological status) and the external environment. Analyses of ascendant family history of atopic disease suggest that AR and atopic dermatitis might share a similar genetic background. OBJECTIVE: To conduct a case-control study in a Chinese Han population to evaluate the potential influence of single nucleotide polymorphisms (SNPs) at FLG, 5q22.1, 11q13.5, 14q11.2 and 20q13.33 on AR. METHODS: Ten SNPs--rs11204971 and rs3126085 at FLG, rs10067777, rs7701890, rs13360927, and rs13361382 at 5q22.1, rs6010620 at 20q13.33, rs7936562 and rs7124842 at 11q13.5, and rs4982958 at 14q11.2 were genotyped in 363 cases and 668 controls using the Sequenom MassArray system. Data were analyzed with PLINK 1.07 software. RESULTS: The T allele of rs4982958 at 14q11.2 was observed to be significantly associated with AR (P = .002, OR = 0.73, P(Bonferront) = .02). Genotype-based association testing revealed that the recessive model might provide the best fit for rs4982958 (P(Bonferroni) = .01). In subphenotype analyses, the rs4982958 T allele was also significantly associated with persistent AR (P = .01) and more than 2 positive skin prick tests (P = .038). CONCLUSION: We identified a novel susceptibility locus 14q11.2 for AR that might bear candidate genes conferring susceptibility to AR and affecting disease phenotypes.

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.

Ultrastructural cytochemical study of enzymes expressed by signet ring cells in gastric cancer.

AIM: To study the ultrastructural localization of five marker enzymes (ALPase, ACPase, G6Pase, TPPase and CCOase) in gastric cancer signet ring cells to demonstrate their biologic behaviors. METHODS: Five marker enzymes were examined in signet ring cells of seven gastric cancer patients by ultrastructural enzyme cytochemical techniques. RESULTS: The number of corresponding organelles and the activities of marker enzymes, especially ACPase and TPPase, increased, leading to stronger mucus synthesis, secretion and digestion in gastric cancer signet ring cells. There was a lack of collagenous fibers in the stroma around the cancer nests. CONCLUSION: Signet ring cell carcinoma is very invasive with metastasis rates due to the secretion of proteolytic enzymes.

[Light and electron microscopic observation of zinc distribution in the carp retina].

Localization of zinc in the carp retina in both light and dark adaptation was investigated using neo-Timm sulfate silver method. The results showed that in light adaptation, zinc was preponderantly present in the outer plexiform layer (OPL). Both terminals of zinc containing photoreceptors and dendrites of bipolar cells usually extend into zinc staining areas in OPL. In dark adaptation, zinc staining in retina is blanched or only appeared in cytoplasmic bodies of few cones. There is no significant difference between dark and light adaptation in the zinc distribution in bipolar, amacrine and ganglion cells. The fact that zinc is perched in the carp retina between photoreceptors and second-order neurons of the visual pathways in OPL in light adaptation and significantly released in dark adaptation suggests that zinc might play some modulatory roles in the visual signal transduction.

The genetic epidemiology of tinea versicolor in China.

To study the clinical and epidemiological profile of Pityriasis versicolor (PV) and to determine the possible genetic model for PV in Chinese Han, we investigated 503 patients with PV who were recruited by a questionnaire method. Statistical analysis, heritability and complex segregation analysis were performed using EPI INFO 6.0, SPSS 10.0, the Falconer method and the SAGE-REGTL programs. In the total 503 PV patients, the mean age of onset was 22.85 +/- 10.36 years. For male and female patients, the peak ages of initial onset were both 20-29 years. A total of 106 (21.1%) patients were reported to have a positive family history of PV. The mean age of onset in males with positive family history was earlier than those with negative family history (t = 3.58, P < 0.01). Higher rate of recurrence and longer duration were seen in the patients with positive family history than those with negative family history. The heritability of PV in first-, second- and third-degree relatives was 48.13%, 40.11% and 27.20% respectively. Based on the REGTL results, the best model was a polygenic additive model for PV.

Association of vitiligo with HLA-A2: a meta-analysis.

BACKGROUND: Linkage and association studies suggest that the human leucocyte antigen (HLA) region may be involved in the genetic susceptibility of vitiligo. HLA-A2 has been reported to be associated with vitiligo in some, but not all, studies. OBJECTIVE: To identify sources of the heterogeneity among studies and to quantify effect estimates, we examined the association of HLA-A2 with vitiligo in a meta-analysis of all observational studies comparing the frequencies of HLA-A2 between vitiligo individuals and controls during 1966-2005. METHODS: The summary odds ratio (OR) was calculated by using a fixed- or a random-effects model. Meta-regression analysis was undertaken to investigate the effects of study characteristics on the pooled OR. RESULTS: Eleven case-controlled studies fulfilled our inclusion criteria. The studies identified a total of 777 patients and 4820 controls. Meta-analysis showed a significantly increased frequency of HLA-A2 in vitiligo among cases [OR = 2.07, 95% confidence interval (CI) 1.67-2.58]. Heterogeneity was explained by the quality of the study and the ethnic background of the participants. Meta-regression analysis further showed that the percentage of familial vitiligo among the subjects had a significant effect on the pooled OR (P = 0.008). No study had a significant effect on the pooled OR and no publication bias presented in the studies analysed (P = 0.688). CONCLUSION: These findings strongly suggest an association between HLA-A2 and vitiligo.

[Relationship between the expression of p53 and C-erbB-2 oncoproteins and biologic behaviors of human mucoepidermal carcinoma of salivary gland]

OBJECTIVE:To study the relationship between the expression of p53 and c-erbB-2 proteins and biologic behaviors of human mucoepidermal carcinoma.METHODS:The expressions of oncogene proteins p53 and c-erbB-2 in 32 cases of human mucoepidermal carcinomas were investigated with microwave immunohistochemistry.RESULTS:p53 and c-erbB-2 oncoproteins in duct epithelial cells around cancer tissues were 10.0% and 15.0%,respectively,but those in the acinar cells affiliated with the salivary gland ducts were negative. The positive rates of p53 oncoprotein and c-erbB-2 oncoprotein in mucoepidermal carcinoma were 40.6% and 46.9%,respectively. Both p53 and c-erbB-2 oncoproteins were expressed in mucous cells,epidermoid cells and intermediate cells of mucoepidermal carcinoma. The expression of p53 and c-erbB-2 oncoproteins in human mucoepidermal carcinoma tissues were related to histological patterns,differentiation degree of cancer and tumor recurrence (P<0.01).CONCLUSION:This study suggested that both p53 and c-erbB-2 on coproteins,as the markers for differentiation of cancer,might be useful in screening progress and evaluating prognosis of patients with mucoepidermal carcinoma.