Identification of Coding Variants in 10q22.1 Associated with Vitiligo in the Chinese Han Population.

Objective: This study aims to identify causal variants associated with vitiligo in an expanded region of 10q22.1. Materials and Methods: We conducted a fine-scale deep analysis of the expanded 10q22.1 region using in a large genome-wide association studies dataset consisting of 1117 cases and 1701 controls through imputation. We selected five nominal coding single nucleotide polymorphisms (SNPs) located in SLC29A3 and CDH23 and genotyped them in an independent cohort of 2479 cases and 2451 controls in a Chinese Han population cohort using the Sequenom MassArray iPLEX1 system. Results: A missense SNP in SLC29A3, rs2252996, showed strong evidence of association with vitiligo (p = 1.34 × 10-8, odds ratio [OR] = 0.82). Three synonymous SNPs (rs1084004 in SLC29A3; rs12218559 and rs10999978 in CDH23) provided suggestive evidence of association for vitiligo (p = 1.69 × 10-6, OR = 0.84; p = 9.47 × 10-5, OR = 1.18; p = 6.90 × 10-4, OR = 1.16, respectively). Stepwise conditional analyses identified two significant independent disease-associated signals from the four SNPs (both p < 0.05; both D' = 0.03; and r2 = 0.00). Conclusion: The study identifies four genetic coding variants in SLC29A3 and CDH23 on 10q22.1 that may contribute to vitiligo susceptibility with one missense variant affecting disease subphenotypes. The presence of multiple genetic variants underscores their significant role in the genetic pathogenesis of the disease.

Serum lipidomic changes and sex differences in androgenetic alopecia.

Background: Androgenetic alopecia (AGA) is the most common form of hair loss. Studies have suggested a potential link to metabolic disorders, but with conflicting results. To elucidate the lipidomics profile and sex-specific variations in AGA, while exploring correlation between AGA and metabolic syndrome (MetS). Methods: The AGA patients (n = 83) and healthy controls (n = 84) were collected in the study. The lipid profiles were analyzed using ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). Serum levels of important factors associated with AGA, namely dihydrotestosterone (DHT), prostaglandin D2 (PGD2) and transforming growth factor-ß1 (TGF-ß1) were quantified using ELISA. Results: Compared with controls, AGA patients had a higher probability of MetS (26.51% vs 11.9%, P < 0.05). Fifty-one differentially expressed lipids were identified in AGA. The kind of triglyceride (TG) were significantly increased, while phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylinositol (PI), and phosphatidylserine (PS) exhibited remarkable decrease. PC (16:2/21:6), PC (34:4p), PE (41:7), PE (44:12), PG (40:9), PI (32:2) and TG (15:0/18:1/18:1) were identified as potential biomarkers of AGA with the highest specificity. The levels of DHT, PGD2 and TGF-ß1 were significantly elevated in AGA. All seven lipids showed significant correlations with DHT, PC (34:4p) and TG (15:0/18:1/18:1) were significantly associated with PGD2, TGF-ß1 displayed exclusively correlation with TG (15:0/18:1/18:1) (all P < 0.05). Furthermore, these lipids were also significantly linked to systolic blood pressure and BMI, while some of them also showed significant associations with total cholesterol and HDL-C. In subgroups, forty-two differentially expressed lipids were identified in male AGA vs male control and eighty-one in female AGA vs female control. PC (16:2/21:6) was the only specific lipids common to both sexes. Conclusions: Aberrant lipid metabolism was observed in AGA, with distinct lipidomic profiles between male and female AGA. The potential biomarkers were closely related to DHT, PGD2, TGF-ß1 and MetS-related indicators. It provides the foundation for revealing the mechanisms of AGA.

Topical bismuth oxide-manganese composite nanospheres alleviate atopic dermatitis-like inflammation.

Atopic dermatitis (AD) is a common skin disease involving important immune mechanisms. There is an unmet need for a treatment for this condition. Herein, we focused on elucidating the role of Bi2-xMnxO3 nanospheres (BM) in alleviating skin inflammation in AD-like C57BL/6 mice. The BM was fabricated via sacrificial templates and its biosafety was systematically evaluated. The BM was applied topically to skin lesions of AD-like C57BL/6 mice. The phenotypic and histological changes in the skin were examined carefully. The responses of barrier proteins, inflammatory cytokines and cells to BM were evaluated in HaCaT cells and AD mouse models. The data demonstrated that BM treatment alleviated the AD phenotypes and decreased the level of inflammatory factors, while increasing the expression of the barrier proteins filaggrin/involucrin in the skin. BM effectively reduced the expression of phosphorylated STAT6, which in turn reduced the expression of GATA3, and further decreased the differentiation ratio of Th2 cells, thereby reducing the expression of IL-4. In conclusion, topical drug therapy with BM provides a safe and effective treatment modality for AD by reducing IL-4 and increasing barrier proteins.

TMEM232 promotes the inflammatory response in atopic dermatitis via the nuclear factor-κB and signal transducer and activator of transcription 3 signalling pathways.

BACKGROUND: Our group previously found that the transmembrane protein 232 (TMEM232) gene was associated with atopic dermatitis (AD) by genome-wide association study and fine mapping study. However, its function is unclear so far. OBJECTIVES: To investigate the roles and mechanisms of TMEM232 in AD. METHODS: The expression of TMEM232 was investigated in skin lesions of patients with AD, the MC903-induced AD mouse model, human primary keratinocytes and immortalized human keratinocyte cell line (HaCaT) cells stimulated with different inflammatory factors. The role of TMEM232 in AD was analysed in HaCaT cells and Tmem232 knockout (Tmem232-/-) mice. Tmem232-specific small interfering RNA (siRNA) was used to evaluate its therapeutic potential in the AD mouse model. RESULTS: The expression of TMEM232 was significantly increased in skin lesions of patients with AD, the MC903-induced AD mouse model and human primary keratinocytes and HaCaT cells stimulated with different inflammatory factors compared with controls. In the presence of MC903, Tmem232-/- mice exhibited significantly reduced dermatitis severity, mast-cell infiltration in the back, and expression of T-helper (Th)1 and Th2-related inflammatory factors in skin tissue compared with wild-type mice. In vitro and in vivo experiments further showed that upregulation of TMEM232 in AD exacerbated the inflammation response through activating the pathway of nuclear factor-κB and signal transducer and activator of transcription (STAT) 3, and was regulated by the interleukin-4/STAT6 axis, which formed a self-amplifying loop. Finally, topical application of Tmem232 siRNA markedly ameliorated AD-like lesions in the AD model. CONCLUSIONS: This study is the first to outline the function of TMEM232. It is involved in regulating inflammation in AD and may be a potential target for AD treatment.

[Genetic diagnosis of a child with Café-au-lait macules and juvenile xanthogranuloma].

OBJECTIVE: To explore the genetic basis for a child with café-au-lait macules and juvenile xanthogranuloma. METHODS: Clinical data and peripheral blood samples of the patient and her family members were collected and subjected to targeted capture and high-throughput sequencing. Candidate variant was verified by Sanger sequencing. RESULTS: A deletional variant in exon 23 of the NF1 gene was detected in the proband. Sanger sequencing has verified it as a de novo variant, which was highly correlated with the clinical manifestations of the patient and her mother. The diagnosis of neurofibromatosis 1 (NF1) was established. The variant was unreported previously. CONCLUSION: Targeted capture and next-generation sequencing combined with Sanger sequencing can facilitate early diagnosis of NF1 and provide a basis for the clinical treatment, genetic counseling and prenatal diagnosis.

Treatment of pyogenic granuloma in children with a 595 nm pulsed dye laser: A retrospective study of 212 patients.

BACKGROUND: Pyogenic granuloma (PG) is a common vascular neoplasm in children. Data on 595 nm pulsed dye lasers for the treatment of PG in children remain scarce. OBJECTIVE: To summarize the clinical characteristics and to evaluate the effectiveness and safety of the 595 nm pulsed dye laser for the treatment of PG in children. STUDY DESIGN: Retrospective case series. METHODS: A retrospective study was performed on 212 patients treated for PG with a 595 nm pulsed dye laser. SPSS version 19.0 was used for statistical analysis. RESULTS: Among all 212 patients treated, 208 showed complete resolution of the lesion, and 4 dropped out after one treatment due to bleeding. A single treatment was sufficient in 139 (66.8%) patients, while two or three treatments were sufficient in 69 (33.2%) patients. Male patients responded better than female patients (χ2 = 7.603, p =0.006). Lesions in the nonorbital region responded better than those in the orbital region (χ2 = 7.445, p =0.006). The size of the lesion affected the effectiveness, and lesions with smaller diameters (t = -5.776, p <0.01) and heights (t = -10.368, p <0.01) showed better results. COMPLICATIONS AND SIDE EFFECTS: Twelve patients (5.8%) were reported to have local complications and side effects, including edematous erythema, slight bleeding, hyperpigmentation, and hypopigmentation. The edematous erythema and slight bleeding disappeared gradually after several days. The localized pigment changes usually resolved spontaneously and disappeared completely after 6 months. CONCLUSIONS: Our experience confirmed the efficacy and safety of the 595 nm pulsed dye laser for the treatment of PG in children.

Confirming the TMEM232 gene associated with atopic dermatitis through targeted capture sequencing.

Atopic dermatitis (AD) is a common and complex skin disorder, and the 5q22.1 region had been reported to be associated with AD. To confirm the susceptibility gene for AD in the 5q22.1 region by haplotype and targeted capture sequencing. The haplotypes were reconstructed with the genotyping data of four SNPs and six deletions from 3624 Chinese Hans AD patients and 5076 controls. The targeted capture sequencing spanning 5q22.1 region was performed in the selected samples. The gene level enrichment analysis was done using loss of function variants. A total of 62 haplotypes were found, and the H15 haplotype had the strongest association with AD (P = 3.92 × 10-10, OR 0.17, 95% CI 0.09-0.32). However, no co-segregation mutation sites were found in the sequencing analysis within the 16 selected samples, while the enrichment analysis indicated that TMEM232 was significantly associated with AD (P = 7.33 × 10-5, OR 0.33, 95% CI 0.19-0.58). This study confirms previous findings that the TMEM232 gene is associated with AD by haplotype analysis and targeted capture sequencing.

A Common Variant at 11q23.3 Is Associated with Susceptibility to Atopic Dermatitis in the Han Chinese Population.

Background: Genome-wide association studies (GWASs) have identified many genetic variants that are risk factors for numerous immune-mediated diseases. In particular, different immune-mediated diseases have been found to share the same susceptibility loci. Therefore, exploring the genetic overlap between atopic dermatitis (AD) and other immune-mediated diseases in more detail may help identify additional shared susceptibility loci among common immune-mediated diseases. Recent evidence suggests that the 11q23.3 locus is a susceptibility locus shared among multiple immune-mediated diseases. Objective: This study was designed to investigated whether SNPs at the chromosome 11q23.3 locus are associated with AD in the Han Chinese population. Methods: In total, 16 SNPs within the 11q23.3 locus were genotyped using TaqMan assays for 1,012 AD cases and 1,362 controls. From these SNPs, we selected rs638893 with an association values of p < 5 × 10-2 for AD for further analysis in an independent replication study using the Sequenom MassARRAY system to genotype an additional (consisting of 1,288 cases and 1,380 controls). The combined analyses were performed in two stages using a meta-analytical method. Results: We identified a common variant at 11q23.3 (rs638893), that was significantly associated (p = 1.58 × 10-3, OR = 1.22) with AD. The genotype-based association analysis revealed that the recessive model provided the best fit for rs638893. Conclusion: Our study identified a variant on chromosome 11q23.3 that likely confers susceptibility to AD, thereby advancing our understanding of the genetic basis of this disease.

An in-depth analysis reveals two new genetic variants on 22q11.2 associated with vitiligo in the Chinese Han population.

BACKGROUND: Vitiligo is a complex disease in which patchy depigmentation is the result of an autoimmune-induced loss of melanocytes in affected regions. On the basis of a genome-wide linkage analysis of vitiligo in the Chinese Han population, we previously showed significant evidence of a linkage between 22q12 and vitiligo. Our aim in the current study was to identify vitiligo susceptibility variants within an expanded region of the 22q12 locus. METHODS AND RESULTS: An in-depth analysis of the expanded region of the 22q12 locus was performed by imputation using a large GWAS dataset consisting of 1117 cases and 1701 controls. Eight nominal SNPs were selected and genotyped in an independent cohort of Chinese Han individuals (2069 patients and 1370 control individuals) by using the Sequenom MassArray iPLEX1 system. The data were analyzed with PLINK 1.07 software. The C allele of rs730669 located in ZDHHC8/RTN4R showed a strong association with vitiligo (P = 3.25 × 10-8, OR = 0.81). The C allele of rs4820338 located in VPREB1 and the A allele of rs2051582 (a SNP reported in our previous study) located in IL2RB showed a suggestive association with vitiligo (P = 1.04 × 10-5, OR = 0.86; P = 1.78 × 10-6, OR = 1.27). The three identified SNPs showed independent associations with vitiligo in a conditional logistic regression analysis (all P < 1.0 × 10-5; all D' < 0.05 and r2 < 1.0 × 10-4). CONCLUSIONS: The study reveals that two novel variants rs730669 (ZDHHC8/RTN4R) and rs4820338 (VPREB1) on 22q11.2 might confer susceptibility to vitiligo and affect disease subphenotypes. The presence of multiple independent variants emphasizes their important roles in the genetic pathogenesis of disease.

Molecular Diagnosis of Neurofibromatosis by Multigene Panel Testing.

Neurofibromatosis (NF) is an autosomal genetic disorder for which early and definite clinical diagnoses are difficult. To identify the diagnosis, five affected probands with suspected NF from unrelated families were included in this study. Molecular analysis was performed using multigene panel testing and Sanger sequencing. Ultradeep sequencing was used to analyze the mutation rate in the tissues from the proband with mosaic mutations. Three different pathogenic variants of the NF1 gene were found in three probands who mainly complained of café-au-lait macules (CALMs), including one frameshift variant c.5072_5073insTATAACTGTAACTCCTGGGTCAGGGAGTACACCAA:p.Tyr1692Ilefs in exon 37, one missense variant c.3826C > T:p.Arg1276Ter in exon 28, and one splicing variant c.4110 + 1G > T at the first base downstream of the 3'-end of exon 30. One NF1 gene mosaic variant was found in a proband who complained of cutaneous neurofibroma with the frameshift variant c.495_498del:p.Thr165fs in exon 5, and ultradeep sequencing showed the highest mutation rate of 10.81% in cutaneous neurofibromas. A frameshift variant, c.36_39del:p.Ser12fs in exon 1 of the NF2 gene, was found in a proband who presented with skin plaques and intracranial neurogenic tumors. All of these pathogenic variants were heterozygous, one was not reported, and one not in Chinese before. This study expands the pathogenic variant spectrum of NF and demonstrates the clinical diagnosis.

Validation of Susceptibility Loci for Vitiligo Identified by GWAS in the Chinese Han Population.

Forty-nine susceptible loci have been reported to be significantly associated with vitiligo by genome-wide association studies (GWASs) in European-derived whites. To date, some of these reported susceptibility loci have not yet been validated in the Chinese Han population. The purpose of this study was to examine whether the 16 reported susceptible loci in European-derived whites were associated with vitiligo in the Chinese Han population. Imputation was performed using our previous GWAS dataset by IMPUTE v2.2.2. The 16 imputed top single-nucleotide polymorphisms (SNPs) with suggestive signals, together with the reported SNPs, were genotyped in a total of 2581 patients and 2579 controls by the Sequenom MassARRAY system. PLINK 2.0 software was used to perform association analysis. The dbSNP database, HaploReg, and eQTL data were adopted to annotate the biological function of the SNPs. Finally, four SNPs from three loci were significantly associated with vitiligo, including rs3747517 (P = 1.29 × 10-3, OR = 0.87) in 2q24.2, rs4807000 (P = 7.78 × 10-24, OR = 0.66) and rs6510827 (P = 3.65 × 10-5, OR = 1.19) in 19p13.3, and rs4822024 (P = 6.37 × 10-10, OR = 0.67) in 22q13.2. According to the dbSNP database, rs3747517 is a missense variant of IFIH1, rs4807000 and rs6510827 are located in TICAM1, and rs4822024 is located 6 kb upstream of TEF. Further bioinformatics analysis by HaploReg and eQTL found that rs4807000, rs6510827, and rs4822024 are involved in regulating gene expression. Our study revealed the strong association of 2q24.2 (rs3747517), 19p13.3 (rs4807000, rs6510827), and 22q13.2 (rs4822024) with the risk of vitiligo in the Chinese Han population, which implicates common factors for vitiligo across different ethnicities, and helps expand the understanding of the genetic basis of this disease.

Quantitative proteomics analysis of young and elderly skin with DIA mass spectrometry reveals new skin aging-related proteins.

Skin aging is a specific manifestation of the physiological aging process that occurs in virtually all organisms. In this study, we used data independent acquisition mass spectrometry to perform a comparative analysis of protein expression in volar forearm skin samples from of 20 healthy young and elderly Chinese individuals. Our quantitative proteomic analysis identified a total of 95 differentially expressed proteins (DEPs) in aged skin compared to young skin. Enrichment analyses of these DEPs (57 upregulated and 38 downregulated proteins) based on the GO, KEGG, and KOG databases revealed functional clusters associated with immunity and inflammation, oxidative stress, biosynthesis and metabolism, proteases, cell proliferation, cell differentiation, and apoptosis. We also found that GAPDH, which was downregulated in aged skin samples, was the top hub gene in a protein-protein interaction network analysis. Some of the DEPs identified herein had been previously correlated with aging of the skin and other organs, while others may represent novel age-related entities. Our non-invasive proteomics analysis of human epidermal proteins may guide future research on skin aging to help develop treatments for age-related skin conditions and rejuvenation.

GWAS Follow-up Study Discovers a Novel Genetic Signal on 10q21.2 for Atopic Dermatitis in Chinese Han Population.

Atopic dermatitis (AD) is a common inflammatory skin disease with high heritability. Two susceptibility loci have been confirmed in our previous AD genome-wide association study (GWAS). To look for additional genetic factors in Chinese Han ethnicity, we performed a large-scale GWAS follow-up study. Forty-nine top single nucleotide polymorphisms (SNPs) that had never been reported previously were genotyped using Sequenom Massarray system in an independent cohort, which consist of northern Chinese (1634 cases and 1263 controls) and southern Chinese (2985 cases and 9526 controls). Association analyses were performed using PLINK 2 software. Three SNPs in northern and ten SNPs in southern were found exhibiting association evidence with AD (P < 0.05). Finally, SNP rs224108 on 10q21.2 showed high significance for AD in joint analysis of GWAS and replication study (P meta = 4.55 × 10-9, OR = 1.21), and was confirmed as an independent genetic marker by Linkage disequilibrium calculation and conditional logistic regression analysis. Bioinformatics analysis strongly suggested that rs224108 may have the potential to alter the target gene expression through non-coding epigenetic regulation effects. Meanwhile, SNP rs11150780 on 17q25.3 was also found suggestive association with AD (P meta = 7.64 × 10-7, OR = 1.18). Our findings confirmed a novel susceptibility signal on 10q21.2 for AD in Chinese Han population and advanced the understanding of the genetic contribution to AD.

Fine mapping and subphenotyping implicates ADRA1B gene variants in psoriasis susceptibility in a Chinese population.

AIM: A genomic region on 5q33.3 lies between and encompasses the IL12B and PTTG1 genes, and contains many potential psoriasis causal variants. We aimed to further examine the influence of variants in and around this region. MATERIALS & METHODS: We used least absolute shrinkage and selection operator (LASSO)-based regression analysis to assess independent contributions of 2171 variants to psoriasis susceptibility and tested them for association with different clinical psoriasis subtypes. RESULTS: We found that ADRA1B gene variants contribute to psoriasis in Chinese population. ADRA1B gene variants have a stronger association with moderate-to-severe disease group and an earlier age at onset of psoriasis than IL-12B and PTTG1 variants. CONCLUSION: The association of variants in the ADRA1B gene with psoriasis could explain why variants in the IL-12B, ADRA1B and PTTG1 gene regions are associated with psoriasis.

Efficacy, safety, and cost-effectiveness of all-trans retinoic acid/Clobetasol Propionate Compound Ointment in the treatment of mild to moderate psoriasis vulgaris: A randomized, single-blind, multicenter clinical trial.

To assess the efficacy, safety, and cost-effectiveness of all-trans retinoic acid/Clobetasol Propionate Compound Ointment and calcipotriol/betamethasone dipropionate ointment in the treatment of mild-to-moderate patients with psoriasis vulgaris. This was a randomized, single-blind, multicenter clinical trial. A total of 240 patients were randomized to receive twice-daily all-trans retinoic acid/Clobetasol Propionate Compound Ointment (treatment group) or once-daily calcipotriol/betamethasone dipropionate ointment (control group) for 4 weeks. The efficacy, safety, and cost-effectiveness were assessed at Weeks 2 and 4. After 4 weeks, both groups showed a significant clinical improvement compared to baseline (88.33% vs. 89.83%, respectively, p = .7112). But PASI 75 response in the treatment group was superior to the control group (44.12% vs. 28.57%, respectively, p = .0200), at Week 4. SSRI improvement rate in the treatment group was also superior to control group (67.11% vs. 59.43%, respectively, p = .0119) at Week 4. All-trans retinoic acid/Clobetasol Propionate Compound Ointment showed a significant clinical improvement in erythema, infiltration, and scales of skin lesions and PASI score compared to baseline. 1.67% of patients (treatment group) reported adverse reactions compared to 2.50% (control group) with no statistical significance. In addition, the cost-effectiveness assessment showed a higher cost-effectiveness of the treatment group compared to the control group in 4 weeks (199.25 vs. 801.51). All-trans retinoic acid/Clobetasol Propionate Compound Ointment was effective and safe in the treatment of psoriasis vulgaris with similar efficacy as calcipotriol/betamethasone dipropionate ointment and lower treatment costs.

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.

A variant on chromosome 2p13.3 is associated with atopic dermatitis in Chinese Han population.

BACKGROUND: Multi-ancestry genome-wide association study (GWAS) has recently identified 11 new susceptibility loci for Atopic dermatitis (AD). The replication of these new susceptibility loci in different populations should not be ignored. OBJECTIVE: To examine whether these 11 new identified susceptibility loci are also associated with AD in the Chinese Han population. METHODS: These 11 variants were imputed using our genome-wide array dataset. The selected SNPs with suggestive signals were genotyped in a large-scale replication study with a total of 4619 cases and 10,789 controls using the Sequenom Massarray system. Association analyses were performed using PLINK 1.07 software. Results were combined across our previous AD-GWAS stage and the replication stage by meta-analysis. Bioinformatic analysis was done to predict the possible causal gene. RESULTS: Of the 11 SNPs investigated, four SNPs showed suggestive association (P<0.05) in our previously published GWAS datasets. Association evidence for an intergenic variant rs112111458 at 2p13.3 with AD was replicated in Chinese Han population (P=7.37×10-7, OR=0.86), showing significance in Meta analysis of GWAS and replication study (Pmeta=8.18×10-08, OR=0.69). Further functional annotation by HaploReg indicated that transcriptional regulation activity exists at this locus for the CD207 gene in skin tissue. CONCLUSIONS: Our study confirmed a previously reported susceptibility loci in the Chinese Han population, which implicates CD207 might be a new susceptibility gene for AD and highlights the crucial role of immune responses in AD.

Association analyses identify two susceptibility loci 5q31 and 5q22.1 for atopic dermatitis in Chinese Han population.

BACKGROUND: Atopic dermatitis (AD) and other atopic diseases often share some common genetic and pathogenic bases. Recent genome-wide association studies (GWAS) have identified several loci associated with atopic diseases, allergic sensitization and asthma in different populations. The aim of this study was to investigate whether these susceptibility loci were related to AD in Chinese Han population. METHODS: Eight single nucleotide polymorphisms (SNPs) from recent atopic diseases and allergic sensitization GWAS were genotyped in 3,013 AD patients and 5,483 healthy controls in Chinese Han population using Sequenom MassArray system. Data was analyzed with PLINK 1.07 software. RESULTS: We identified that the susceptibility loci at 5q31 (RAD50/IL13, rs2158177, P = 1.08×10-3, OR = 1.15) and 5q22.1 (TSLP, rs1837253, P = 2.66×10-3, OR = 0.91) were significantly associated with AD. Genotype-based association testing revealed that the dominant model provided the best fit for both rs2158177 (P = 3.75×10-3) and rs1837253 (P = 5.30×10-3). Pathway analysis conformed that both loci were associated with the JAK-STAT signaling pathway. CONCLUSIONS: We identified two susceptibility loci 5q31 and 5q22.1 for AD that might bear candidate genes conferring susceptibility to AD.