Genome‐wide association study of psoriasis in an Egyptian population

Psoriasis is a chronic inflammatory disorder of the skin, with genetic factors reportedly involved in the disease pathogenesis. Numerous studies reported psoriasis candidate genes. However, these tend to involve mostly in the European and Asian populations. Here, we report the first genome‐wide association study (GWAS) in an Egyptian population, identifying susceptibility variants for psoriasis using a two‐stage case‐control design. In the first discovery stage, we carried out a genome‐wide association analysis using the Infinium^® Global Screening Array‐24 v1.0, on 253 cases and 449 control samples of Egyptian descent. In the second replication stage, 26 single‐nucleotide polymorphisms (SNPs) were selected for replication in additional 321 cases and 253 controls. In concordance with the findings from previous studies on other populations, we found a genome‐wide significant association between the MHC locus and the disease at rs12199223 (P_comb = 6.57 × 10^?18) and rs1265181 (P_comb = 1.03 × 10^?10). Additionally, we identified a novel significant association with the disease at locus, 4q32.1 (rs12650590, P_comb = 4.49 × 10^?08) in the vicinity of gene GUCY1A3, and multiple suggestive associations, for example rs10832027 (P_comb = 7.28 × 10^?06) and rs3770019 (P_comb = 1.02 × 10^?05). This proposes the existence of important interethnic genetic differences in psoriasis susceptibility. Further studies are necessary to elucidate the downstream pathways of the new candidate loci.     

Susceptibility variants on chromosome 7p21.1 suggest HDAC9 as a new candidate gene for male-pattern baldness

Background Male‐pattern baldness (androgenetic alopecia, AGA) is the most common form of hair loss among humans. Research has shown that it is caused by genetic factors. Numerous studies have unequivocally identified two major genetic risk loci for AGA: the X‐chromosomal AR/EDA2R locus, and the PAX1/FOXA2 locus on chromosome 20. Objectives To identify further candidate genes for AGA, and thus gain further insights into this phenotype. Methods A German sample of 581 severely affected cases and 617 controls was used to perform a genome‐wide association study. The identified associated locus was further analysed by fine‐mapping, and then independently replicated in an Australian sample. Expression and pathway analyses were performed to characterize the susceptibility gene identified. Results The most significant association signal was obtained for rs756853 (P = 1·64 × 10^?7), which is located intronically in the histone deacetylase 9 (HDAC9) gene. Fine‐mapping and a family‐based analysis revealed that rs756853 and the 6‐kb distal rs2249817 were the most highly associated single nucleotide polymorphisms. The association finding was replicated in an independent Australian sample, when the analysis was restricted to severely affected cases and unaffected controls (P = 0·026). Analysis of rs2249817 in a combined sample of severely affected German and Australian cases and unaffected controls revealed a strong association signal (P = 9·09 × 10^?8). Tissue expression studies demonstrated HDAC9 expression in various tissues, including tissues of relevance to AGA. No strong genotypic effects were observed in genotype‐specific expression or splice studies. Pathway analyses supported the hypothesis that HDAC9 plays a functional role in AGA via interaction with the AR gene. Conclusions The present study suggests that HDAC9 is the third AGA susceptibility gene.     

Variants in SELL,MRPS36P2, TP63, DDB2, CACNA1H,ADAM19, GNAI1, CDH13 and GABRG2 interact to confer risk of acne in Chinese population

Acne vulgaris is a common skin disease characterized by chronic inflammation of the pilosebaceous unit resulting from androgen‐induced increased sebum production, altered keratinization, inflammation and bacterial colonization of hair follicles by propionibacterium acnes. Our previous genome‐wide association study on acne has identified two new susceptibility loci. To search for potential gene–gene interactions and investigate the best‐fit association models for the single nucleotide polymorphisms (SNP) from these interacting genes, we implemented logistic regression analysis in the combined sample of 2916 cases with severe acne and 4716 controls. The most significant association evidence was observed under an additive model for rs6896064 and under a dominant model the rest of these SNP. Significant interactions between these SNP were observed in this study: the SELL × MRPS36P2 (P_adjusted = 4.15 × 10^?10), TP63 × DDB2 (P_adjusted = 7.62 × 10^?08), DDB2 × CACNA1H (P_adjusted = 1.89 × 10^?07), ADAM19 × GNAI1 × CDH13 (P_adjusted = 1.22 × 10^?04) and ADAM19 × GABRG2 × GNAI2 × CDH13 (P_{ad justed} = 6.33 × 10^?05). These results may contribute to our understanding of acne genetic etiology and account for the additional risk of certain patients.     

Vitamin D receptor gene polymorphisms are associated with psoriasis susceptibility and the clinical response to calcipotriol in psoriatic patients

Psoriasis is a common genetic disease characterized by hyperproliferation and disordered maturation of keratinocytes. To date, many association studies between psoriasis and VDR gene have been conducted, but the results are controversial. Furthermore, vitamin D₃ analogue has anti-psoriatic activity; however, the clinical response is variable. This study was conducted to explore whether VDR gene polymorphisms are associated with psoriasis susceptibility and clinical response to calcipotriol in psoriatic patients. A total of 110 patients and 183 controls were genotyped for VDR gene polymorphisms rs2228570, rs731236, rs1544410 and rs7975232 by LDR method. SNP-based and haplotype-based association analyses were subsequently performed. Patients with PASI < 3 were treated with calcipotriol ointment monotherapy. After 6 weeks of therapy, the correlations between efficacy and the genotypes of each polymorphism were evaluated. The results showed that for rs7975232, allele A was significantly over-represented in psoriasis patients relative to controls (39.09% vs. 27.05%, OR (95% CI) = 1.731 (1.213-2.471)), and compared with the reference CC genotype, the following ORs were observed: AA genotype OR = 2.404 (95% CI: 1.085-5.328; P = .034) and GA genotype OR = 2.143 (95% CI: 1.283-3.579; P = .005). Haplotype analyses showed that the rs2228570/rs731236/rs1544410/rs7975232 CTGA was significantly over-represented in psoriasis patients compared with controls (OR (95% CI)=1.907 (1.132-3.214); P = .020). Among the patients with PASI < 3, the response rates to calcipotriol were significantly higher in patients with rs7975232 CC genotypes than in those with other genotypes (x² = 9.172, P = .010). These data suggest that VDR polymorphisms are associated with psoriasis susceptibility and clinical response to calcipotriol in psoriatic patients.     

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.     

Novel gene identified in an exome‐wide association study of tanning dependence

Growing evidence suggests that some individuals may exhibit symptoms of dependence to ultraviolet light, a known carcinogen, in the context of tanning. Genetic associations with tanning dependence (TD) have not yet been explored. We conducted an exome‐wide association study in 79 individuals who exhibited symptoms of TD and 213 individuals with volitional exposure to ultraviolet light, but who were not TD based on three TD scales. A total of 300 000 mostly exomic single nucleotide polymorphisms primarily in coding regions were assessed using an Affymetrix Axiom array. We performed a gene burden test with Bonferroni correction for the number of genes examined (P < 0.05/14 904 = 3.36 × 10^?6). One gene, patched domain containing 2 (PTCHD2), yielded a statistically significant P‐value of 2.5 × 10^?6 (OR = 0.27) with fewer individuals classified as TD having a minor allele at this locus. These results require replication, but are the first to support a specific genetic association with TD.     

Investigation of 20 non‐HLA (human leucocyte antigen) psoriasis susceptibility loci in Chinese patients with psoriatic arthritis and psoriasis vulgaris

Background Recently, a number of non‐HLA (human leucocyte antigen) psoriasis genetic susceptibility loci have been identified through genome‐wide association studies, but data on their association with psoriatic arthritis (PsA) are lacking. Objectives To investigate recently identified psoriasis susceptibility loci in a cohort of Chinese patients with PsA, psoriasis vulgaris (PsV) and healthy controls. Methods Twenty single‐nucleotide polymorphisms (SNPs) from 20 loci were selected for genotyping in 379 patients with PsA, 595 patients with PsV and 1181 healthy controls using the MassARRAY platform (Sequenom, San Diego, CA, U.S.A.). Data handling, quality control and association were performed using PLINK software, v. 1.07. The Cochran–Armitage trend test was used to test the genotype–phenotype association. Results PsA showed a significant association with markers at TNIP1 (rs17728338, P = 2·20 × 10^?8), IL28RA (rs4649203, P = 5·04 × 10^?6), IL12B (rs2082412, P = 3·82 × 10^?5), ERAP1 (rs27524, P = 1·25 × 10^?3), PTTG1 (rs2431697, P = 1·22 × 10^?3) and GJB2 (rs3751385, P = 1·48 × 10^?3) when compared with the control group. In PsV a significant association was found for IL28RA (rs4649203, P = 9·53 × 10^?7), TNIP1 (rs17728338, P = 1·21 × 10^?4) and ERAP1 (rs27524, P = 1·17 × 10^?3). The allele frequencies were not statistically different between PsA and PsV except for SNPs at IL12B and ZNF816A with a nominal P‐value of 0·04 and 0·01, respectively. Conclusions This study provides evidence for the involvement of ERAP1, IL28RA, GJB2 and PTTG1 loci in PsA susceptibility and confirmed the previously reported association with PsA and PsV. These results support the hypothesis that genetic aetiology of psoriasis is the same in both PsA and PsV and also support the higher genetic component of PsA than PsV.     

Association of rs3783641 single‐nucleotide polymorphism in GTP cyclohydrolase 1 gene with post‐herpetic neuralgia

Post‐herpetic neuralgia (PHN) is a well‐established clinical problem with potential severe personal and socioeconomic implications. GTP cyclohydrolase 1 (GCH1) gene, which encodes the rate‐limiting enzyme in tetrahydrobiopterin synthesis, has been strongly implicated to be associated with neuropathic pain in previous animal and human studies. The rs3783641 (T > A) single‐nucleotide polymorphism (SNP) in the GCH1 gene is functional. Here we examine the association between rs3783641 and PHN. A total of 292 subjects including 103 PHN patients, 87 herpes zoster (HZ) patients and 102 healthy controls were enrolled in this study. The rs3783641 polymorphisms were detected via the high‐resolution melting curve (HRM) method. There were statistical differences between PHN group and the other two groups in genotype distribution (P = 0.029 and 0.017, respectively) and allele frequency (P = 0.032 and 0.005, respectively) of rs3783641. The proportion of subjects with AA genotype in the PHN group was significantly lower compared to HZ group and control group (P = 0.026 and 0.016, respectively). The frequency of A allele was lower in the PHN group than in control group (P = 0.005), and the frequency of T allele in the PHN group was higher than in HZ group and control group (P = 0.001 and 0.003, respectively). The results of this study suggest that the rs3783641 SNP in the GCH1 gene is associated with PHN, and the AA genotype showed a protective effect in PHN.     

Identification of a possible susceptibility locus for UVB‐induced skin tanning phenotype in Korean females using genomewide association study

A two‐stage genomewide association (GWA) analysis was conducted to investigate the genetic factors influencing ultraviolet (UV)‐induced skin pigmentation in Korean females after UV exposure. Previously, a GWA study evaluating ~500 000 single nucleotide polymorphisms (SNPs) in 99 Korean females identified eight SNPs that were highly associated with tanning ability. To confirm these associations, we genotyped the SNPs in an independent replication study (112 Korean females). We found that a novel SNP in the intron of the WW domain‐containing oxidoreductase (WWOX) gene yielded significant replicated associations with skin tanning ability (P‐value = 1.16 × 10^?4). To understand the functional consequences of this locus located in the non‐coding region, we investigated the role of WWOX in human melanocytes using a recombinant adenovirus expressing a microRNA specific for WWOX. Inhibition of WWOX expression significantly increased the expression and activity of tyrosinase in human melanocytes. Taken together, our results suggest that genetic variants in the intronic region of WWOX could be determinants in the UV‐induced tanning ability of Korean females. WWOX represents a new candidate gene to evaluate the molecular basis of the UV‐induced tanning ability in individuals.     

Genome-wide association analysis of psoriasis patients treated with anti-TNF drugs

While anti-TNF therapies are effective against psoriasis, 30%–50% of patients do not show an adequate response to these drugs. Different candidate-gene pharmacogenetics studies have identified single nucleotide polymorphisms that may predict anti-TNF drugs response in psoriasis. Nevertheless, only one paper has undertaken a pharmacogenomic approach failing to find significant biomarkers of biological drug response along the whole genome. Furthermore, most of the pharmacogenetic candidate biomarkers identified previously have not been confirmed in a different cohort of patients. The objective of this study was to find biomarkers that could predict anti-TNF drugs response along the whole genome and validate biomarkers identified previously. A genome-wide association study (GWAS) was performed using the Human Omni Express-8 v1.2 Beadchips in 243 psoriasis patients treated with anti-TNF drugs. This study was multicentric and did not interfere with clinical practice. Associations between single nucleotide polymorphisms (SNP) and PASI75 (a 75% reduction with respect to baseline PASI) at 3 months were evaluated. Imputation was performed using SNPs with R² > 0.7. There were two SNPs located in NPFFR2 that were close to the significant threshold of 5 × 10⁻⁸. These data suggest that NPFFR2 might be associated with anti-TNF drug response. However, further studies involving a larger cohort of patients are needed in order to confirm these results.     

Comparison of sagging at the cheek and lower eyelid between male and female faces

Background: Facial sagging is a well‐known morphological feature associated with aging and reduced dermal elasticity. Its morphological characteristics and mechanism have been studied in females, but it is unclear whether or not there is a gender difference. Aims: The aim of this study was to clarify the morphological characteristics of sagging and the mechanism of sagging formation in male faces as compared with female faces, focusing on changes in dermal elasticity. Methods: Faces of 98 healthy Japanese male volunteers, in their 20s–60s, were photographed at an angle of 45°. Upper and lower cheek sagging severity was evaluated by using photograph‐based grading criteria. In addition, new photograph‐based grading criteria of sagging severity at the lower eyelid were established and used. Dermal elasticity was measured using a non‐invasive, in vivo suction skin elasticity meter, Cutometer^®. Furthermore, photographs of 108 healthy Japanese female volunteers in their 20s–60s were used to compare the difference in the morphological characteristics of sagging between males and females. Results: Male facial sagging was prominent at the lower eyelid, upper cheek and lower cheek. Sagging severity in the upper and lower cheek was almost the same between males and females at all ages, whereas sagging at the lower eyelid in males was significantly more severe than that in females after middle age. Although dermal extensibility (U_f) was not related to age, total deformation recovery (U_a), ?(amount of deformation) ?(U_f?U_a), overall elasticity of the skin including creep and creep recovery (U_a/U_f), net elasticity excluding viscoelastic creep (U_r/U_e), ratio of elastic recovery to total deformation (U_r/U_f) and ?(ratio of viscoelastic to elastic distention) ?(U_v/U_e) were all significantly negatively related to age in both men and women. Furthermore, as in female faces, male facial sagging was significantly negatively related to dermal elasticity parameters, such as ?(U_f?U_a), U_a/U_f, U_r/U_e and U_r/U_f. Conclusion: These results indicate that the morphology and areas of sagging in male faces are similar to those in females in the cheek, but sagging at the lower eyelid is more severe in males after middle age. Furthermore, the dermal elasticity of male facial skin decreased with age similar to that of females, and may therefore be associated with the sagging formation in male faces.     

TNF‐α and IL‐10 gene polymorphisms show a weak association with pemphigus vulgaris in the Slovak population

Backround Pemphigus vulgaris is a rare chronic autoimmune disease of skin and mucous membranes, with several cytokines participating in its development. The role of their gene polymorphisms in susceptibility to the disease is, however, not fully understood. Objective The aim of our case‐control study was to investigate whether some of 22 single nucleotide polymorphisms (SNPs) in 13 cytokine genes (IL‐1α, IL‐1β, IL‐1RI, IL‐1Ra, IL‐4Rα, IL‐12, IFN‐γ, TGF‐β1, TNF‐α, IL‐2, IL‐4, IL‐6 and IL‐10) are associated with pemphigus vulgaris in the Slovak population. Methods DNA samples were obtained from 34 pemphigus vulgaris patients and 140 healthy controls of Slovak origin. Cytokine gene SNPs were determined using the polymerase chain reaction with sequence‐specific primers (PCR‐SSP) method. Results We found a weak association between pemphigus vulgaris and polymorphic variants in TNF‐α and IL‐10 genes only, with haplotypes TNF‐α–308G/–238G and IL‐10 –1082A/–819C/–592C being significantly overrepresented in pemphigus vulgaris patients (TNF‐α GG: 94.12% vs. 82.86%, P = 0.0216; IL‐10 ACC: 44.12% vs. 30.00%, P = 0.0309). Conclusions Our preliminary results suggest that certain TNF‐α and IL‐10 gene polymorphisms might contribute to genetic susceptibility to pemphigus vulgaris; however, their overall impact on disease development will be rather limited.     

Genetic prediction of the effectiveness of biologics for psoriasis treatment

Anti‐tumor necrosis factor (TNF)‐α therapy is used for the treatment of psoriasis, with varying outcomes. However, the specific cause of inadequate response or treatment failure remains unknown. The aim of the present study was to identify useful clinical biomarkers for predicting therapeutic responses or to serve as new drug targets for refractory psoriasis cases. We performed a genome‐wide association study (GWAS) of 65 psoriasis patients who were prospectively followed after beginning anti‐TNF‐α therapy using Human Omni Express‐8 v1.2 Beadchips. Patients were enrolled at the dermatology departments of Kobe University Hospital and six collaborative hospitals. Associations between single nucleotide polymorphisms (SNP) and changes in the Psoriasis Area and Severity Index (PASI) after 12 weeks of treatment were evaluated. After genome data collection and quality control, a total of 731 442 SNPs were identified in 65 Asian psoriasis patients who were treated with adalimumab or infliximab. Here, we present 10 SNPs, such as those in JAG2 and ADRA2A, that were associated with treatment responses to anti‐TNF‐α agents (strongest effect, P < 7.11E‐06). This is the first GWAS to examine SNP associated with treatment responses in psoriasis patients. In addition, we identified other SNP that exhibited potential associations with anti‐TNF‐α treatment response, which merit further study. Of these, rs11096957 on TLR10, which is associated with increased TNF‐α production, was previously reported to be associated with treatment responses to TNF‐α inhibitors.     

Genetic support for the role of the NLRP3 inflammasome in psoriasis susceptibility

NACHT leucine‐rich repeat‐ and PYD‐containing (NLRP)3 protein controls the inflammasome by regulating caspase‐1 activity and interleukin (IL)‐1β processing. The contribution of IL‐1β in the pathogenesis of psoriasis is well recognized. Polymorphisms in NLRP3 and caspase recruitment domain–containing protein (CARD)8, a negative regulator of caspase‐1 activity, have been associated with susceptibility to common inflammatory diseases, such as Crohn's disease and rheumatoid arthritis. To investigate the role for genetic variants in the NLRP3 inflammasome in psoriasis susceptibility. In a patient sample comprising 1988 individuals from 491 families and 1002 healthy controls, genotypes for four selected single‐nucleotide polymorphisms (SNPs) in NLRP3 (three SNPs) and CARD8 (one SNP) were determined by TaqMan^® Allelic Discrimination. Using the transmission disequilibrium test (TDT), a significant increase in the transmission of the NLRP3 rs10733113G genotype to a subgroup of patients with more widespread psoriasis was demonstrated (P = 0.015). Using logistic regression analysis in 741 patients with psoriasis and 1002 controls, the CARD8 rs2043211 genotype was significantly different in cases and controls in overall terms [OR 1.3 (1.1–1.5), P = 0.004] and for both genders. Our data support the hypothesis that the inflammasome plays a role in psoriasis susceptibility.     

A single nucleotide polymorphism rs9468925 of MHC region is associated with clinical features of generalized vitiligo in Chinese Han population

Background Vitiligo has been found to be associated with different HLA antigens in different ethnic groups. In our previous genome‐wide association study (GWAS), we identified independent association signal of rs9468925 (P = 2.21 × 10^?33, OR = 0.74) within HLA‐C‐HLA‐B region. Objectives To explore the association between rs9468925 polymorphism within MHC and the clinical features of generalized vitiligo. Methods The study, using 5566 cases and 6462 controls from previous GWA study investigated the single and combined (GA + GG) genotypic distribution of rs9468925 in subsets of vitiligo patients having different clinical features. We performed a QTL analysis (quantitative trait locus) for age of onset with genotype of rs9468925. Results The GA + GG genotypic distribution of SNP rs9468925 tested with an additive model was found to be significantly different in subgroups of patients of >20 vs. <20 years old (genotypic P = 2.57 × 10^?4, combined P = 3.0 × 10^?3, OR = 0.77, 95% CI: 0.64–0.92), and in patients with different clinical subtypes of vitiligo (genotypic P = 0.03, combined P = 5.0 × 10^?3). However, there was no statistical significance for familial history, halo nevi involvement and autoimmune disease involvement. Conclusions Allele G of rs9468925 on HLA‐C‐HLA‐B may be associated with a higher risk of vitiligo. Our study showed a significant genotypic variation between patients with age of onset ≤20 years and age of onset >20 years. Obvious clinical differences of generalized vitiligo related to genotypic variation found in the Chinese Han population were confirmed in this study.     

C‐reactive protein (CRP) rs3093059C predicts poor mizolastine response in chronic spontaneous urticaria patients with elevated serum CRP level

Chronic spontaneous urticaria (CSU) is a frequent disorder with recurrent itchy wheals and/or angioedema, and nearly 35% patients respond poorly to non‐sedating H1 antihistamine treatment. CRP gene encodes the C‐reactive protein, which is involved in the pathogenesis of CSU. To investigate the impacts of CRP polymorphisms on the susceptibility and therapeutic efficacy in the South Han CSU patients, we enrolled 145 CSU patients in our study. After 4‐week non‐sedating H1 antihistamine monotherapy treatment, more than 50% reduction of the severity score is considered as effective, or else non‐effective. The CRP rs3093059T/C and rs2794521G/A genotypes of patients were determined by Sequenom MassARRAY. Functional studies including relative luciferase assay and β‐hexosaminidase assay were conducted in HEK293T cells or RBL‐2H3 cells to explore the function of variants. Forty (62.50%) CSU patients were effective when treated with mizolastine, and 55 (72.4%) patients were effective in the desloratadine group. We found that the patients carried with rs3093059TT genotype were significantly associated with good response (OR = 4.20, P = 0.015), had lower serum CRP, IL‐6 and TNF‐α levels than the CT/CC genotypes. In vitro, the rs3093059C allele exhibited significantly higher luciferase activity than wild allele (P < 0.001). From the β‐hexosaminidase assay, we observed the inhibiting degranulation effects by mizolastine and this effect is weakened when with a higher dose CRP in RBL‐2H3 cells. Our findings suggested that CSU patients carrying the rs3093059C allele may respond poorly to mizolastine with elevated serum CRP level.     

Rs4948496 within ARID5B gene is associated with clinical features of systemic lupus erythematosus in the Chinese Han population

In our previous meta‐analysis of genome‐wide association study, we identified the single nucleotide polymorphism (SNP) rs4948496 (P = 5.1 × 10^?11, odds ratio [OR] = 0.85) within the ARID5B gene associated with systemic lupus erythematosus (SLE) in a Chinese population. To investigate its association with disease subphenotypes, we further analyzed the genotype data of rs4948496 in 4348 cases and 6679 controls from our previous meta‐analysis and an independent replication cohort in this study. The SNP rs4948496 was significantly associated with SLE (P = 1.61 × 10^?5, OR = 0.88, 95% confidence interval [CI] = 0.83–0.93) in our group. In case‐only study, the genotype of rs4948496 was associated with antinuclear antibodies (P = 0.03, OR = 0.81, 95% CI = 0.68–0.98) and anti‐RNP (P = 0.03, OR = 0.86, 95% CI = 0.76–0.99). This study showed that rs4948496 in ARID5B is associated with several subphenotypes of SLE and this gene may cause the complicacy of clinical features.     

Analysis of filaggrin 2 gene polymorphisms in patients with atopic dermatitis

BackgroundPolymorphisms of the filaggrin 2 gene (rs 12568784 and rs 16899374) are associated with persistent atopic dermatitis in African American patients. Filaggrin 2 is a protein with a function similar to filaggrin and also encoded in the epidermal differentiation complex on chromosome 1q21.ObjectiveTo evaluate the polymorphisms in the filaggrin 2 gene (rs 12568784 and rs 16899374) in children and adults with atopic dermatitis and to verify the association of these with the severity of the clinical picture, presence of other allergic diseases, and socio-demographic factors.MethodThe study was carried out with patients and control group. Questionnaires were used to evaluate ethnicity, sex, age, family history, scoring, atopic dermatitis (SCORAD), among other parameters. Genotyping of the filaggrin 2 gene was performed by real-time polymerase chain reaction.ResultsForty-eight patients and 83 controls were evaluated. No correlation was found between the variables studied in patients with atopic dermatitis and polymorphisms, no significant difference between the prevalence of polymorphisms in the patients and in the control group p > 0.05.Study limitsThe exclusive use of self-reported ethnicity information and the sample size.ResultsThe results of this work can be an incentive for the study of the polymorphisms in atopic dermaititis, considering the characteristic of the Brazilian multi ethnic population.ConclusionThis is an unpublished work in Brazil and the first study in the world to have a control group to evaluate alterations in the gene of filaggrin 2.     

Association of the novel susceptible locus rs9266150 with clinical features of psoriasis vulgaris in the Chinese Han population

Psoriasis is a chronic multifactorial disease and is considered to be strongly associated with the major histocompatibility complex (MHC) region. We have discovered an independent, novel and susceptible psoriasis risk HLA loci, rs9266150; P = 4.52 × 10^?9 for the first time. In this study, we aimed to verify the relationship between the susceptible locus and the subphenotypes of psoriasis vulgaris (PV), including geographic location, gender, age of onset, family history and present skin lesion types (chronic plaque and guttate). To investigate the distribution and association of the rs9266150 gene with clinical phenotypes of PV in Chinese Han population, we conducted an analysis in case‐control and case‐only subjects in the 9906 controls and 8744 cases by MHC targeted sequencing stratified analysis in this study. Significant associations were found with a northern geographic location in the case‐only (P = 1.97 × 10^?4) and the subphenotype‐control analyses (P = 5.57 × 10^?5), males in the case‐only (P = 4.77 × 10^?3) and the subphenotype‐control analyses (P = 7.31 × 10^?4), and guttate psoriasis in the case‐only (P = 4.08 × 10^?3) and the subphenotype‐control analyses (P = 1.27 × 10^?3). There were no significant differences observed between the age of onset (OR = 1.062, 95% CI: 0.9725‐1.16, P = 1.8 × 10^?1) and the family history of psoriasis (OR = 0.981, 95% CI: 0.9048‐1.064, P = 6.43 × 10^?1). The recessive model provided the best fit for rs9266150 (P = 4.38 × 10^?7). Our results implied that rs9266150 might not only play an important role in the development of psoriasis, but also be positively associated with the geographic location, gender and present skin lesion in the Chinese population.