Association between HLA-DRB1 polymorphisms and pemphigus vulgaris: a meta-analysis

Background Several studies have reported that HLA‐DRB1 may be correlated with pemphigus vulgaris (PV), but most have been based on small samples and the results remain inconsistent and unclear. Objectives To investigate the correlation between DRB1 and PV by a meta‐analysis of case–control/nonfamily studies. Methods PubMed, Wiley Online Library, ScienceDirect, Google Scholar, Cochrane Library, Chinese National Knowledge Infrastructure and Wanfang databases were searched for studies including: (i) ‘pemphigus’; and (ii) ‘human leukocyte antigen’, ‘HLA’, ‘major histocompatibility complex’, ‘MHC’ or ‘DRB1’. Eighteen selected studies were used in meta‐analyses to evaluate DRB1 alleles and phenotypes by calculating the respective odds ratios (ORs) and 95% confidence intervals (CIs). Stratified meta‐analyses and meta‐regression analysis were also conducted. Results The frequencies of three genotypes (allele and phenotype, respectively) were significantly increased in PV: DRB1*04 [P‐value for comparability (Pc) < 0·00001, OR 3·61, 95% CI 2·28–5·71; Pc = 0·0002, OR 4·14, 95% CI 1·98–8·65], DRB1*08 (Pc = 0·03, OR 2·25, 95% CI 1·07–4·70; Pc = 0·0003, OR 2·46, 95% CI 1·51–4·01) and DRB1*14 (Pc < 0·00001, OR 6·47, 95% CI 4·52–9·26; Pc < 0·00001, OR 9·68, 95% CI 4·47–20·98). Three others (allele and phenotype, respectively) were significantly decreased in PV: DRB1*03 (Pc < 0·00001, OR 0·28, 95% CI 0·19–0·41; Pc = 0·0001, OR 0·25, 95% CI 0·12–0·51), DRB1*07 (Pc = 0·004, OR 0·45, 95% CI 0·26–0·78; Pc = 0·0002, OR 0·27, 95% CI 0·14–0·54) and DRB1*15 (Pc = 0·001, OR 0·35, 95% CI 0·18–0·66; Pc = 0·002, OR 0·32, 95% CI 0·16–0·65). Ethnicity partially explained the heterogeneity of DRB1*07, DRB1*08 and DRB1*14 phenotypes. Conclusions Our findings suggest that DRB1*04, DRB1*08 and DRB1*14 are statistically significant susceptibility factors for PV. Conversely, DRB1*03, DRB1*07 and DRB1*15 may be negatively associated with PV. Specific HLA‐DRB1 types may influence the susceptibility or resistance to PV, which needs further investigations.     

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.     

Association between HLA-B*58:01 allele and severe cutaneous adverse reactions with allopurinol in Han Chinese in Hong Kong

Background Allopurinol has been reported as a common cause of severe cutaneous adverse reactions (SCARs). Recent studies in various populations suggest that HLA‐B*58:01 is a strong genetic marker for allopurinol‐induced SCAR, especially in populations with a high frequency of HLA‐B*58:01. Objectives To confirm the association link between HLA‐B*58:01 and hypersensitivity reactions attributed to allopurinol use in Han Chinese patients in Hong Kong. Methods We performed a case–control study to investigate whether the HLA‐B*58:01 allele predisposes to allopurinol‐induced SCAR in Han Chinese patients in Hong Kong. The HLA‐B*58:01 genotyping was performed in 20 patients with allopurinol‐induced SCAR or erythema multiforme major (EMM; n = 1) and in 30 patients tolerant to allopurinol. Results All of the 19 patients with allopurinol‐induced SCAR examined but not the patient with EMM carried HLA‐B*58:01 whereas only four (13%) of the control patients had this allele. The positive rate of the HLA‐B*58:01 was significantly higher in the cases than in the allopurinol‐tolerant control group [odds ratio (OR) 123·5, 95% confidence interval (CI) 12·8–1195·1; P < 1 × 10^?4] and was even higher after removal of the patient with EMM (OR 229·7, 95% CI 11·7–4520·4). The sensitivity and specificity of the HLA‐B*58:01 allele for prediction of allopurinol‐induced SCAR were 100% and 86·7%, respectively. Conclusions This study confirmed the strong association between the HLA‐B*58:01 and allopurinol‐induced SCAR in Hong Kong Han Chinese patients. A screening test for the HLA‐B*58:01 allele should effectively reduce the risk for allopurinol‐induced SCAR in Chinese populations.     

Association of HLA-DQA1 and DQB1 alleles with alolpecia areata in Chinese Hans

Accumulative evidences have shown that certain HLA loci are associated with alopecia areata (AA), but with existing differences in ethnic distribution. No report has ever been published about this in Chinese Hans. To investigate whether HLA-DQA1 and DQB1 alleles are associated with AA, and the correlation of the HLA profile with age of onset, severity, duration of current attack, recurrence and family history of AA in Chinese Hans. The polymerase chain reaction–sequence-specific primer (PCR-SSP) method was used to analyze the distribution of HLA-DQA1 and DQB1 alleles in 192 patients with AA and 273 healthy controls in Chinese Hans. The significant increased frequencies of HLA-DQA1*0104 (OR=3.38, P _c<0.001), HLA-DQB1*0604 (OR=5.17, P _c=0.006) and HLA-DQA1*0606 (OR=3.73, P _c<0.001) were observed in patients compared with controls. The DQA1*0104-DQB1*0604, DQA1*0104-DQB1*0606, and DQA1*0302-DQB1*0606 were found as high-risk haplotypes in developing AA in this study. HLA-DQA1*0104 (OR=5.31, P _c < 0.001) and -DQB1*0604 (OR=5.56, P _c=0.015) were more prevalent only in AA patients with long duration than controls. The frequencies of HLA-DQB1*0604 (OR=5.42, P _c=0.009) and -DQB1*0606 (OR=4.11, P _c<0.001) were obviously increased in patients less than 50% scalp hair loss. No locus was merely associated with early onset, severe involvement, recurrence and a positive family history of AA. This study demonstrated the positive association of HLA-DQA1 and DQB1 alleles and haplotypes with AA. There may be differences in genetic background in patients with different duration.     

Class II MHC typing in pemphigoid gestationis

Pemphigoid gestationis (PG) is a rare, autoimmune skin disease associated with pregnancy or the immediate postpartum period, previously shown to be associated with the HLA class II antigens DR3 and DR 4. Advances in molecular analytical techniques now allow the identification of HLA alleles previously difficult to define by serological assays. Unsuspected polymorphism within the HLA-DR 3 and DR 4 classes can, therefore, be identified. The aim of our study was to apply these newer techniques to the question of genetic predisposition in PG by re-evaluating the association with DR 3 and by studying a possible link with DQ. We have investigated by restriction fragment length polymorphism, the DQA, and by sequence specified oligonucleotide probing the DQB and DRB 1 (HLA DR) specificities of 41 women with immunofluorescence-confirmed PG. The principal finding of this study is that there is an association between PG and DRB 1*0301 (DR3) and DRB 1*0401/040X (DR4). Although there is also an increase (P= 0.06) in the concurrent presence of both antigens, this appears to be due to the association with either antigen alone. We also found an increase in the frequency of DQA1*2 (P= 0.016 vs. control) and a decrease in frequency of DQB 1*0201 (P= 0.022 vs. controls) and DQB1*0602 (P= 0.026 vs. controls).     

Comparisons of clinical features of HLA‐DRB1*07 positive and negative vitiligo patients in Chinese Han population

Background Human leucocyte antigen (HLA)‐II alleles have been found to be associated with vitiligo in different populations, and several studies also suggested that HLA class II alleles/haplotypes were associated with a different type vitiligo. Of HLA class II alleles, DRB1*07 has consistently shown a positive association with vitiligo in Chinese Han population. Objective To further explore the relationship between DRB1*07 and vitiligo and to evaluate the DRB1*07 effect on the clinical features of vitiligo in Chinese Han population. Methods This study investigated DRB1*07 allele distribution in 1178 unrelated Chinese vitiligo patients and 1743 healthy controls using polymerase chain reaction/sequence specific primer method and observed clinical differences between DRB1*07 positive and DRB1*07 negative patients. Results The analysis of the 1178 cases and 1743 controls revealed a highly association between DRB1*07 allele and vitiligo [odds ratio (OR) = 1.97, P = 2.13 × 10^?17]. DRB1*07 positive patients had early disease onset (OR = 1.49, P = 0.001), higher frequency of family history (OR = 1.44, P = 0.006) compared with DRB1*07 negative patients. Conclusions The DRB1*07 showed significant association with vitiligo in the study population. This study confirmed that DRB1*07 positive patients had some obvious clinical differences from DRB1*07 negative patients in the Chinese Han population.     

Association of HLA alleles and haplotypes with vitiligo in Moroccan patients: a case–control study

The aim of this study was to identify HLA class II alleles that may be involved in vitiligo genetic susceptibility in the Moroccan population and to determine susceptible and protective HLA alleles/haplotypes in vitiligo. One-hundred unrelated vitiligo patients and 300 healthy unrelated controls were studied for HLA class II alleles by polymerase chain reaction-sequence-specific primers. The phenotypic frequency of DRB1*07 (OR = 2.23, p _c = 0.014) was significantly higher, while that of DRB1*03 (OR = 0.40, p _c = 0.014) was significantly lower in patients than in controls. Haplotype DRB1*07–DQB1*02 (OR = 2.25, p _c = 0.024) was positively associated with vitiligo patients, while haplotype DRB1*03–DQB1*02 (OR = 0.35, p _c = 0.012) was negatively associated with this group. Vitiligo patients with positive family history and negative anti-thyroid peroxidase antibody (anti-TPO) have an extremely high phenotype frequency of DRB1*07–DQB1*02 haplotype (OR = 2.91, p _c = 0.048 and OR = 2.62, p _c = 0.00475, respectively). DRB1*03–DQB1*02 (OR = 0.32, p _c = 0.048 and OR = 0.38, p _c = 0.048, respectively) was negatively associated with patients without a family history and negative anti-TPO. This study demonstrated the positive association of HLA class II alleles and haplotypes with vitiligo in the Moroccan population. There may be differences in HLA haplotypes distribution in patients according to family history and anti-TPO profile.     

Correlation between HLA and pityriasis rosea susceptibility in Brazilian blacks

Objectives The human leucocyte antigen (HLA) has been related to susceptibility factors in several diseases. This study aimed to determine the potential genetic susceptibility of patients with pityriasis rosea (PR) through HLA molecular typing analysis. Methods The method of choice was polymerase chain reaction with sequence‐specific primers (PCR‐SSP) using low‐resolution typing kits, with determination of the alleles class I (HLA‐A, HLA‐B and HLA‐C) and class II (HLA‐DRB1, DRB3, DRB4, DRB5 and DQB1) performed in 30 Afro‐Brazilian PR‐diagnosed patients and 45 healthy individuals as the control group (PR‐C). Results Analysis of the HLA typing results showed that the relative risk (RR) of 4.00 [95% confidence interval (95% CI) 1.20–13.28, two‐tailed P = 0.018] for allele HLA‐DQB1*04 class II, detected in 33.3% of PR patients, was significant. By contrast, in the control group only 11.1% of subjects had that allele. Three out of six B*51 alleles and three out of six B*53 alleles detected in PR patients were found, together with the allele DQB1*04. Conclusion We suggest that alleles DQB1*04 may be involved in the genetic susceptibility of PR based on the significant predominance of those alleles observed in the black PR patients. We also recommend that more studies are conducted on populations of other ethnic origins, preferentially with higher resolution techniques of DNA typing.     

Association of HLA class I and class II alleles with bullous pemphigoid in Chinese Hans

Background

Bullous pemphigoid (BP) is one of the most common autoimmune skin diseases. Associations of genes, especially human leukocyte antigen (HLA)-DQ alleles, with BP indicate that genetic predisposition contributes to the disease.

Polymorphisms in human histamine receptor H4 gene are associated with atopic dermatitis

Background Atopic dermatitis (AD) is a chronic skin disease affecting more than 15% of children and 2% of adults. A strong connection between genetic factors and AD has been described for a long time. Histamine receptor H4 (HRH4) has been shown to be related to different kinds of allergic and autoimmune disorders. However, an association between HRH4 and AD has not yet been reported. Objectives To examine a possible association between HRH4 and AD. Methods Genomic DNA from 301 patients with AD and 313 healthy controls was extracted and three exons of HRH4 were sequenced. Results We found three new single nucleotide polymorphisms (SNPs) in HRH4 which were significantly associated with AD: ss142022671 [odds ratio (OR) 1·87, 95% confidence interval (CI) 1·24–2·81; P = 0·002], ss142022677 (OR 4·40, 95% CI 2·42–8·00; P = 1·5 × 10^?7) and ss142022679 (OR 4·26, 95% CI 2·38–7·61; P = 1·3 × 10^?7). The SNPs ss142022677 and ss142022679 were found to be in strong linkage disequilibrium (D’ = 0·98; r² = 0·92). Two‐SNP haplotype analysis (ss142022677 and ss142022679) showed that the major AA haplotype was protective against AD (OR 0·22, 95% CI 0·12–0·40; P = 3·1 × 10^?8) and the minor TT haplotype was significantly associated with AD (OR 4·13, 95% CI 2·27–7·54; P = 6·6 × 10^?7). In addition, in a three‐SNP haplotype analysis (ss142022671, ss142022677 and ss142022679), the major TAA haplotype was protective against AD (OR 0·46, 95% CI 0·31–0·69; P = 0·0001), while the complementary ATT haplotype was found to be significantly associated with AD (OR 3·81, 95% CI 2·03–7·14; P = 8·3 × 10^?6). Conclusions Polymorphisms of ss142022671, ss142022677 and ss142022679 in HRH4 are associated with AD.     

Tunisian endemic pemphigus foliaceus is associated with the HLA-DR3 gene: anti-desmoglein 1 antibody-positive healthy subjects bear protective alleles

Background  Pemphigus foliaceus is an autoimmune blistering skin disease that partly results from genetic factors, especially human leucocyte antigen (HLA) class II genes.
Objectives  The aim of the study was to determine the HLA DR/DQ markers of susceptibility and protection in the Tunisian endemic form.
Methods  Genomic DNA from 90 patients with pemphigus foliaceus recruited from all parts of the country and matched by age, sex and geographical origin with 270 healthy individuals, was genotyped.
Results  Firstly, when the whole patient population was studied, DRB1*03 , DQB1*0302 and DRB1*04 alleles were significantly associated with the disease while a significant decrease of, in particular, DRB1*11 and DQB1*0301 was observed in patients compared with controls. DRB1*0301 was the dominant allele in DR3-positive patients and controls, while DRB1*0402 was found in 42% of DR4-positive patients. Secondly, when the HLA DR/DQ allele distribution was studied after dividing patients according to their geographical origin, the southern group, which consisted exclusively of patients with the endemic form of the disease, showed the same associations as the whole pemphigus foliaceus population, particularly with DRB1*03 . In the northern group, only the DRB1*04 and DQB1*0301 alleles were found to be associated. Interestingly, anti-desmoglein 1 antibody-positive healthy controls did not carry susceptibility alleles but, in contrast, most carried negatively associated alleles.
Conclusions  These observations indicate that a particular genetic background characterizes the Tunisian endemic form of pemphigus foliaceus and that HLA class II genes control the pathogenic properties of the autoimmune response rather than the initial breakage of B-cell tolerance.     

The association between HLA DR, DQ antigens, and vulval lichen sclerosus in the UK: HLA DRB112 and its associated DRB112/DQB10301/04/09/010 haplotype confers susceptibility to vulval lichen sclerosus, and HLA DRB10301/04 and its associated DRB10301/04/DQB10201/02/03 haplotype protects from vulval lichen sclerosus

Lichen sclerosus (LS) is considered to have an immunogenetic background. Several small studies, using serological typing, have reported that HLA-DR11, DR12, and DQ7 were increased in LS, with DR17 less frequent. This study aimed to validate and detect new HLA-DR and DQ associations with LS in females and its characteristic clinical parameters. The cases, 187 female LS patients, and 354 healthy controls were all UK North Europeans. PCR-sequence specific primers method was applied to genotype the HLA-DR, DQ polymorphisms that correspond to 17 serologically defined DR and seven DQ antigens. Statistical analysis was performed with two-tailed Fisher's exact test with Bonferroni adjustment (p value after Bonferrroni adjustment, Pc). We found increased frequency of DRB1*12 (DR12) (11.2%vs 2.5%, pc < 0.01) and the haplotype DRB1*12/DQB1*0301/04/09/010 (11.2%vs 2.5%, p < 0.001, pc < 0.05), and a lower frequency of DRB1*0301/04 (DR17) (11.8%vs 25.8%, pc < 0.01) and the haplotype DRB1*03/DQB1*02DRB1*0301/DQB1*0201/02/03 (11.2%vs 24.6%, pc < 0.0001) in patients compared with controls. HLA DR and DQ antigens were not associated with time of onset of disease, site of involvement, structural changes of genitals, and response to treatment with potent topical steroids. In conclusion, HLA-DR and DQ antigens or their haplotypes appear to be involved in both susceptibility to and protection from LS.     

Association of HLA loci alleles and antigens in Saudi patients with vitiligo

HLA complex is composed of several closely linked loci, each containing several alleles, yielding a high expression of polymorphism. Vitiligo, a commonly acquired dermatological disorder, has been associated with different HLA antigens in different ethnic groups. In this study, HLA classes I (HLA-A, B, and C) and II (HLA-DR, DQ) antigens/alleles were analyzed in a group of 80 Saudi subjects consisting of vitiligo patients (40) and matched controls (40). The frequency of antigens of various HLA loci was tested using two-stage microcytotoxicity assays, while the frequency of alleles of HLA-DR was screened by polymerase chain reaction/sequence specific primers (PCR/SSP) method. The frequencies of HLA-B7, B15, Bw6, Cw6, Cw7, and DRB4*010101 were found to be significantly higher in vitiligo patients compared to controls [P = 0.029, 0.015, 0.033, 0.009, 0.043, and 0.015, respectively, with relative risk (RR) ≥ 3, etiologic fraction (EF) ≥ 0.4]. On the other hand, HLA-A9, B5, DQ1, and DRB3*010101 were significantly decreased in vitiligo patients compared to healthy Saudis [P = 0.008, 0.004, 0.028, and 0.04, respectively, with RR < 1 and preventive fraction (PF) < 0.5]. Among the patients, the highest allele frequency was noted for DRB4*010101(70%), while in controls it was for DRB3*010101 (72.5%). These results for antigens and allele frequency of various HLA Loci in vitiligo patients and control subjects suggested that HLA-B7, Bw6, Cw6, Cw7, and DRB4*010101 could be susceptible to vitiligo, while HLA-A9, B5, DQ1, and DRB3*010101 might be negatively associated with the development of vitiligo in Saudis.     

HLA-DR and DQ polymorphisms in bullous pemphigoid from northern China

Bullous pemphigoid (BP) is an autoimmune disease mediated by autoantibodies against hemidesmosome components. This study used PCR-sequence-specific primers to genotype polymorphisms in HLA-DR and DQ in 25 BP patients and 57 normal controls from northern China. We found lower frequencies of DRB1*08 (DR8) and DRB1*08/DQB1*06 (DR8/DQ6) haplotypes in BP patients than in controls (4.08% vs. 15.19% and 1.54% vs. 13.82%, respectively; P < 0.05), suggesting a protective role for DR8 and DR8/DQ6 haplotypes in BP patients from northern China; there were no statistical differences among other alleles tested. This result is strikingly different from previous reports that DQB1*0301 is associated with BP in Caucasian patients and DRB1*1101, DQB1*0302, DRB1*04/DQA1*0301/DQB1*0302 and DRB1*1101/ DQA1*0505/DQB1*0302 with Japanese BP patients. Ethnic differences in the polymorphic composition of the HLA-DR and DQ genes may influence genetic susceptibility to BP.     

Multiple basal cell carcinomas: no association with HLA-DRB, HLA-DQAI or HLA-DQBI in Swedish patients

Summary Many diseases with autoimmune features are associated with alleles of the human leucocyte antigen (HLA). However, few if any malignant disorders have reproducibly been shown to be HLA-associated. In three independent studies, using serological tissue typing techniques, an increase of the HLA class II specificity DR1 has been found in patients with multiple basal cell carcinomas. These observations prompted us to determine the frequencies of DRB1, DQA1, and DQB1 alleles by high-resolution genomic tissue-typing methods, including subdivision of the serological DR 1 specificity in the four sequence-defined alleles, DRB1*0101 to DRB1*0104, in 50 unrelated Swedish patients with a history of four or more basal cell carcinomas and 250 healthy controls. The frequency of DR1 was the same in patients and controls (18%). All DR1-positive patients and controls carried the DQA1* 0101 and DQBI*0501 alleles. Six of the nine DR1-positive patients were DRB1*0101-positive. one DRB1*0102 and two carried the DRB1*0103 allele. This distribution of DRB1*01 alleles did not differ from the one found in the controls. We conclude that genetic factors associated with the HLA class II region do not contribute significantly to the aetiology of multiple basal cell carcinomas.     

HLA markers in familial Lichen Sclerosus

Background: Lichen sclerosus (LS) has been identified with increased frequency in families,often associated with HLA markers, mainly DQ7. A genetic co‐etiology seems likely in this setting. Moreover, there is an association of LS with autoimmune disorders, such as the presence of anti‐thyroid peroxidase autoantibodies (anti‐TPO), a hallmark of autoimmune thyroid diseases. Patients and Methods: In 3 families affected by LS, we verified their HLA markers, and identified previously undiagnosed cases of LS and autoimmune disorders. 30 individuals were examined with history, skin biopsy, HLA class I and II typing by PCR‐SSP, and measurement of anti‐TPO, free thyroxine and thyroidstimulating hormones (TSH) levels. Results: There were 8 cases of LS, 50 % of them anti‐TPO+. Autoimmune disorders were found in 40 % (total) and in 87.5 % of those affected. Most common HLA markers were B*15, B*57, CW*03, CW*07, CW*18, DRB1*04, DRB1*07, DRB4*. The three latter have been previously associated with LS. Conclusion: New cases of LS and autoimmune disorders can be detected in first degree relatives of patients with LS. The presence of anti‐TPO antibodies strongly suggests autoimmune thyroiditis. There is intra‐familial association between the haplotype HLA‐B*15 ‐DRB1*04 ‐DRB4* and anti‐TPO,emphasizing their link with thyroiditis. New familial approaches might help to make clear the pathogenesis of LS and its association with autoimmune diseases.     

Identification of PTPN22, ST6GAL1 and JAZF1 as psoriasis risk genes demonstrates shared pathogenesis between psoriasis and diabetes

The biological connections between psoriasis and diabetes have been suggested by epidemiological, immunological and genetic studies. To identify additional shared susceptibility loci and investigate shared pathogenesis between these two diseases, we genotyped 89 reported diabetes susceptibility loci in 4456 psoriasis cases and 6027 controls of Chinese population using the MassARRAY system from Sequenom. We discovered three significant associations at rs6679677 on 1p13.2 (P=6.15×10^?5, OR=5.07), rs16861329 on 3q27.3 (P=2.02×10^?4, OR=0.87) and rs849135 on 7p15.1 (P=6.59×10^?9, OR=1.78), which suggested PTPN22, ST6GAL1 and JAZF1 as novel susceptibility genes for psoriasis in Chinese population. Our findings implicated the involvement of T‐cell receptor signalling pathway in the pathogenesis of psoriasis and further confirmed the shared genetic susceptibility between psoriasis and diabetes.     

The genetic basis of alopecia areata: HLA associations with patchy alopecia areata versus alopecia totalis and alopecia universalis

Many diseases, notably those having a strong autoimmune component, have been shown to have an association with specific human leukocyte antigens (HLA). The molecular basis for this genetic association with disease is the fact that HLA bind and present peptides derived from self and foreign protein antigens to the immune system for recognition and activation of the immune response. Previous studies with heterogeneous groups of alopecia areata (AA) patients have suggested associations with some HLA class I and class II antigens. For this study we selected only patients with long-standing disease and stratified them into two groups by strict definitions of duration and extent of disease: those with patchy AA and those with either alopecia totalis (AT) or alopecia universalis (AU). The patients were tissue typed for HLA class II antigens by biomolecular methods that provided antigen discrimination at an allele level. More than 80% of all of the AA patients typed were positive for the antigen DQB1*03 (DQ3), suggesting that this antigen is a marker for general susceptibility to AA. In addition, two other antigens were found significantly increased in frequency only in the group of AT/AU patients, DRB1*0401 (DR4) and DQB1*0301(DQ7). This strongly suggests that the two clinical types of AA, namely patchy AA versus AT/AU, can be distinguished by a genetically based predisposition to extent of disease.     

Paediatric-onset psoriasis is associated with ERAP1 and IL23R loci, LCE3C_LCE3B deletion and HLA-C*06

Summary Background Recent genome‐wide association studies have identified several genetic risk factors for psoriasis, but data on their association with age at onset are lacking. Objectives To compare the association between known risk alleles and psoriasis in well‐defined cohorts with paediatric‐ and adult‐onset psoriasis. Methods Based on previous studies we selected seven genes and loci associated with psoriasis. Patients with paediatric‐onset (< 18 years) and adult‐onset psoriasis (≥ 18 years) and controls were genotyped. Genotype frequencies were compared between controls (n = 450) and all cases (n = 217), and between controls and cases stratified for confirmed age at onset (paediatric onset n = 80, adult onset n = 85). Results Paediatric‐onset psoriasis showed a significant association with single nucleotide polymorphisms in the ERAP1 (P = 0·042) and IL23R loci (P = 0·042), LCE3C_LCE3B‐del (P = 0·003) and HLA‐C*06 (P = 1·72 × 10^?19) when compared with the control group. A significant association of these four genes was also demonstrated when all psoriasis cases were compared with controls. In adult‐onset psoriasis a significant association was found for HLA‐C*06 (P = 5·11 × 10^?6) and for LCE3C_LCE3B‐del (P = 0·042). No associations were found for the IFIH1, IL12B and TRAF3IP2 loci. Conclusions Notwithstanding the small cohort sizes, we demonstrated an association with established and recently discovered genetic risk factors in paediatric‐onset psoriasis including genes involved in epidermal barrier function and adaptive immunity. Our data suggest that heritable factors may play a more important role in paediatric‐onset psoriasis than in adult‐onset psoriasis.