Factors associated with non-pathogenic antibodies against desmoglein-3 in pemphigus foliaceus.

BACKGROUND: Anti-desmoglein (Dsg)1 is produced in pemphigus foliaceus (PF), affecting exclusively the skin. Pemphigus vulgaris (PV) shows the production of anti-Dsg3 in the mucosal form, and anti-Dsg1 and 3 in the mucocutaneous form. Anti-Dsg3 autoantibodies have been rarely reported in PF. OBJECTIVES: To determine the factors associated with the production and pathogenicity of anti-Dsg3 in PF. METHODS: Comparative analytical study of three patients groups: 16 PF-anti-Dsg3+, and 42 PF-anti-Dsg3(-) and 22 PV treatment-naïve cases. Serum was used in the anti-Dsg1 and 3 ELISA, and in immunoblotting (IB) with human epidermis extract. The expression of Dsg1 and 3 in paraffin sections was analyzed by immunohistochemistry (IHC). HLA-DRB1 alleles were compiled from a database. RESULTS: In the PF-anti-Dsg3+ group: age range similar to that of the PV group (p > 0.9999); predominance of the generalized form of PF (p = 0.002); anti-Dsg3 titers lower than those of PV (p < 0.0001); IB confirmed Dsg3 identification in one (8.33%) of 12 patients; IHC showed exclusive cytoplasmic internalization of Dsg1; HLA-DRB1 alleles of susceptibility to PF, with the absence of alleles associated with PV, in the five typed patients. STUDY LIMITATIONS: Most of the patients in the PF-anti-Dsg3+ group were undergoing treatment. CONCLUSION: The presence of anti-Dsg3 antibodies in PF was related to older age (comparable to that of PV) and the generalized form of PF. The non-pathogenicity of anti-Dsg3 antibodies in PF can be attributed to the low serum anti-Dsg3 titers, the lack of Dsg3 internalization as detected by IHC, and the absence of PV-associated HLA-DRB1 alleles.

Epigenome-wide methylation haplotype association analysis identified HLA-DRB1, HLA-DRB5 and HLA-DQB1 as risk factors for rheumatoid arthritis.

The aim of this study was to compare nonrandom associations between physically adjacent single methylation polymorphism loci among rheumatoid arthritis (RA) and normal subjects for investigating RA-risk methylation haplotypes (meplotype). With 354 ACPA-positive RA patients and 335 normal controls selected from a case-control study based on Swedish population, we conducted the first RA epigenome-wide meplotype association study using our software EWAS2.0, mainly including (i) converted the ß value to methylation genotype (menotype) data, (ii) identified methylation disequilibrium (MD) block, (iii) calculated frequent of each meplotypes in MD block and performed case-control association test and (iv) screened for RA-risk meplotypes by odd ratio (OR) and p-values. Ultimately, 545 meplotypes on 334 MD blocks were identified significantly associated with RA (p-value < .05). These meplotypes were mapped to 329 candidate genes related to RA. Subsequently, combined with gene optimization, eight RA-risk meplotypes were identified on three risk genes: HLA-DRB1, HLA-DRB5 and HLA-DQB1. Our results reported the relationship between DNA methylation pattern on HLA-DQB1 and the risk of RA for the first time, demonstrating the co-demethylation of 'cg22984282' and 'cg13423887' on HLA-DQB1 gene (meplotype UU, p-value = 2.90E - 6, OR = 1.68, 95% CI = [1.35, 2.10]) may increase the risk of RA. Our results demonstrates the potential of methylation haplotype analysis to identify RA-related genes from a new perspective and its applicability to the study of other disease.

The Role of HLA-DRB1 Alleles in Pulmonary Cystic Fibrosis.

Cystic fibrosis (CF) is the most common lethal autosomal recessive disease in white Caucasians. It affects many organs including the lung, pancreas, and liver. Whilst CF is a monogenic disease, several studies revealed a complex relationship between genotype and clinical phenotype of diseases. We examined the expression of human leukocyte antigen (HLA) class II alleles among Iranian CF patients with disease-related microbial infection. This study was conducted on 50 hospitalized CF patients (27 males, 23 females aged 15.5±6.5 years), and 50 healthy age- and gender-matched control subjects. 5ml whole blood was harvested and after isolation of genomic DNA, HLA-DRB1 subtypes were determined by single specific primer polymerase chain reaction methods. HLA-DRB1*10 was less frequent and HLA-DRB1*04 and HLA-DRB1*11 was the most frequent allele in CF patients, but none reached significance. HLA-DRB1*04 allele was frequently seen among16 CF patients with high serum IgE levels (430.25±219.7 IU/mL) and 27 CF patients that were positive for Pseudomonas aeruginosa colonization. A total of 31 CF patients had candida Albicans colonization in whom HLA-DRB1*11 was mostly seen. A total of 3 CF patients had allergic bronchopulmonary aspergillosis and two were diabetic. The DR4 and DR11 serotypes that recognize the HLA-DRB1*04 and HLA-DRB1*11 gene products respectively are not significantly enriched in the Iranian CF population. Further research should be conducted on DR4 and DR11 in CF patients to understand their possible role in infection and IgE expression.

HLA-DQA1*04: 01 is related to a higher multiple sclerosis lesion load on T2/Flair MRI sequences / O HLA-DQA1*04: 01 está relacionado com uma alta carga lesional na ressonância magnética em T2/Flair nos pacientes com esclerose múltipla

ABSTRACT Background: The genetic predisposition to multiple sclerosis (MS) is associated with HLA alleles, especially HLA-DRB1*15:01. Objective: To identify associations between findings in magnetic resonance imaging (MRI) and genetic features in a Brazilian cohort of patients with MS. Methods: We retrospectively studied data from 95 consecutive patients with MS. Two independent observers who were blinded to the clinical data identified black holes and enhanced lesions on T1 MRI sequences, and counted and measured contrast-enhanced lesions on T2 and Flair (fluid attenuation inversion recovery) sequences. Cases were classified according to lesion size, number, and volume. The HLA-DRB1, HLA-DQB1, and HLA-DQA1 alleles, and the rs4774, rs3087456, rs6897932, rs731236, and rs1033182 single nucleotide polymorphisms were identified by polymerase chain reaction amplification with sequence-specific primers using the One Lambda Inc. Kit, Canoga Park, CA, USA. Results: Patients with the HLA-DQA1*04:01 allele had lesion load (adjusted for age, sex, and MS duration) above median compared with patients with other HLA-DQA1 alleles (p=0.02). There were no differences among all the other HLA alleles and single nucleotide polymorphisms and lesion load. Conclusions: The correlation of the HLA-DQA1*04:01 allele with a higher lesion load on T2/Flair MRI sequences suggests that the presence of this allele is associated with the risk of greater MS severity.

RESUMO Antecedentes: A predisposição genética para a esclerose múltipla (EM) está associada a alelos HLA, principalmente o HLA-DRB1*15:01. Objetivo: Identificar associações entre lesões na ressonância magnética e características genéticas em uma coorte brasileira de pacientes com EM. Métodos: Estudamos retrospectivamente os dados de 95 pacientes consecutivos com EM. Dois observadores independentes que desconheciam os dados clínicos identificaram "black holes" e lesões realçadas pelo contraste nas sequências de ressonância magnética T1 e contaram e mediram as lesões nas sequências T2 e FLAIR (fluid attenuated inversion recovery). Os casos foram classificados de acordo com tamanho, número e volume da lesão. Os alelos HLA-DRB1, HLA-DQB1 e HLA-DQA1 e os polimorfismos de nucleotídeo único rs4774, rs3087456, rs6897932, rs731236 e rs1033182 foram identificados por amplificação de reação em cadeia da polimerase com iniciadores específicos de sequência usando o kit One Lambda Inc., Canoga Park, CA, EUA. Resultados: Os pacientes com alelo HLA-DQA1*04:01 apresentaram carga de lesão (ajustada para idade, sexo e duração da EM) acima da mediana em comparação com outros pacientes com demais alelos HLA-DQA1 (p=0,02). Não houve diferenças entre todos os outros alelos HLA e polimorfismos de nucleotídeo único e carga lesional. Conclusões: A correlação do alelo HLA-DQA1*04:01 com maior carga de lesão nas sequências de RM em T2 sugere que a presença desse alelo pode estar associada ao risco de maior gravidade da EM.

Clinical Relevance of HLA-DRB1 and -DQB1 Alleles in Iranian Systemic Lupus Erythematosus Patients.

Given the potential link between genetic risk factors and clinical features of systemic lupus erythematosus (SLE), this study aimed to explore the relationship between human leukocyte antigen (HLA)-DRB1/DQB1 alleles and haplotypes and clinical sub-phenotypes of the disease in a group of Iranian SLE patients. HLA-DRB1 and HLA-DQB1 alleles were determined by PCR-SSP in 127 SLE patients and 153 ethnically-matched healthy controls. The relationships between various clinical manifestations and HLA alleles/haplotypes were analyzed in the patients. We observed the positive associations of DRB1*07 and DRB1*07-DQB1*02 haplotypes with articular and pulmonary involvement (p=0.006 and p<0.001 respectively), DRB1*03 and DQB1*02 alleles, and DRB1*03-DQB1*02 haplotypes with cutaneous (p=0.03, p=0.004 and p=0.02 respectively) and renal involvement, and DRB1*13 as well as DRB1*13-DQB1*06 haplotypes with renal involvement. Conversely, negative associations of DRB1*13 with cutaneous and gastrointestinal disorders (p=0.004 and p=0.02 respectively) and DRB1*01 with renal involvement (p=0.03) were found in our patients. Patients carrying susceptible HLA-DRB1 alleles had a higher risk for expression of cutaneous involvement (p=0.03), anti-coagulant antibody development (p=0.01), and a lower risk for pulmonary disorders compared to patients' negatives for susceptible alleles (p=0.04). Our findings on associations between HLA risk allele (DRB1*03) as well as non-risk alleles with particular clinical manifestations and between the potentially protective allele (DRB1*01) and protection against renal involvement indicate the important role of HLA class II genes in predisposing of specific serological and clinical features of SLE disease which could be implicative for therapeutic applications and better management of SLE patients.

A case-control study of HLA alleles in Brazilian patients with Melkersson-Rosenthal syndrome.

Melkersson-Rosenthal syndrome (MRS) is a neuromucocutaneous disease that manifests by the triad of recurrent orofacial edema (frequently as cheilitis granulomatosa), relapsing facial paralysis and plicated tongue. The cause of MRS remains unknown, but genetic predisposal and a relationship with inflammatory bowel disease are suspected. The objective of this research was to compare the frequency of class I and II HLA alleles in patients with a confirmed diagnosis of MRS with those of a healthy control group. We conduct a case-control study and typed of HLA A, B, C, DR, and DQ using molecular techniques. The study included 36 patients with MRS and 297 patients in the control group. There was an increase in the expression of HLA A*02 (p = 0.0269; OR: 1,79 [1,045-2,973]), HLA DRB1*11 (p < 0,0001; OR: 4,009 [2,214-7,277]), HLA DRB1*13 (not statistically significant) and HLA DQB1*03 (p = 0,0177; OR: 1,829 [1,122-2,978]) and low levels of HLA A*01 (p = 0.0046; OR: 0,097 [0,009-0,538]), HLA DRB1*04 (p = 0.0274; OR: 0,228 [0,053-0,844]), HLA DRB1*07 (p = 0,0091; OR: 0,183 [0,043-0,670]) and HLA DQB1*02 (p = 0.0051; OR: 0,312 [0,143-0,721]) in MRS patients compared with the control group. Crohn disease (CD) patients had disparate genetic profiles versus those with MRS. This single-institution study had a small cohort, because this disease is rare. Conclusions: There is a genetic predisposition toward MRS, involving associated and protective genes.

Polimorfismos do gene HLA-DRB1 em pacientes pediátricos com hepatite autoimune tipo 1 e hepatite autoimune associada à colangite autoimune / Hla-drb1 gene polymorphisms in pediatric patients with type 1 autoimmune hepatitis and type 1 autoimmune hepatitis overlap syndrome with autoimmune cholangitis

ABSTRACT BACKGROUND: Autoimmune hepatitis (AIH) is a rare chronic inflammatory liver disease associated with a loss of immunological tolerance to self-antigens. Susceptibility to AIH is partially determined by the presence of genes related to human leukocyte antigen (HLA), mainly allelic variants of DRB1. OBJECTIVE: The purpose of this study was to investigate the frequencies of the polymorphisms in HLA-DRB1 gene in children and adolescents with type 1 AIH and type 1 AIH overlap syndrome with autoimmune cholangitis (overlap syndrome, OS) in comparison to healthy sex and age-matched individuals (control group). METHODS: This is a cross-sectional study of 25 pediatric patients diagnosed with type 1 AIH and 18 with OS. Fifty-seven healthy individuals were included as controls. The polymorphisms of the HLA-DRB1 gene were evaluated by PCR and included HLA-DRB1*03, HLA-DRB1*04, HLA-DRB1*07, and HLA-DRB1*13. RESULTS: Our results showed that the presence of the allele HLA-DRB1*13 increased the chance of autoimmune cholangitis (OR=3.96, CI 1.07 to 14.61, P=0.04). The HLA-DRB1*04 and HLA- DRB1*07 have no association with the AIH and autoimmune cholangitis in a young sample. CONCLUSION: This work demonstrates an association of the main polymorphisms in the HLA-DRB1 gene to AIH with or without cholangitis in a Brazilian sample.

RESUMO CONTEXTO: Hepatite autoimune (HAI) é uma doença hepática inflamatória crônica, rara, associada à perda da tolerância imunológica aos auto-antígenos. A susceptibilidade à HAI é parcialmente determinada pela presença de genes relacionados ao antígeno leucocitário humano (HLA), principalmente variantes alélicas do DRB1. OBJETIVO: O objetivo deste estudo foi investigar a frequência de polimorfismos no gene HLA-DRB1 em crianças e adolescentes com HAI tipo 1 e HAI tipo 1 associada à colangite autoimune, em comparação com indivíduos saudáveis pareados por sexo e idade (grupo controle). MÉTODOS: Este é um estudo transversal de 25 pacientes pediátricos com diagnóstico de HAI tipo 1 e 18 com HAI associada à colangite autoimune. Cinquenta e sete indivíduos saudáveis foram incluídos como controles. Os polimorfismos do gene HLA-DRB1 foram avaliados por PCR e incluíram HLA-DRB1*03, HLA-DRB1*04, HLA-DRB1*07 e HLA-DRB1*13. RESULTADOS: Nossos resultados mostraram que a presença do alelo HLA-DRB1*13 aumentou a chance de colangite autoimune (OR=3,96; IC 1,07 a 14,61; P=0,04). O HLA-DRB1*04 e o HLA-DRB1*07 não apresentam associação com a HAI e colangite autoimune no grupo de pacientes mais jovens. CONCLUSÃO: Este trabalho demonstra uma associação dos principais polimorfismos no gene HLA-DRB1 à HAI com ou sem colangite na população brasileira.

Autism & Gluten: The Proof By Regression!

Investigators from different clinical and research centers from Paris, France studied the polymorphisms of the HLA class II loci in an autistic population. Through a case control design, they looked for the distribution of HLA class II alleles, genotypes and haplotypes in Autism Spectrum Disorders (ASD) patients meeting DSM-IV TR criteria versus healthy controls (HC).

Association analysis between HLA-DRB1 alleles and pemphigus vulgaris in a Han population in Sichuan / 中华皮肤科杂志

Objective To investigate the association between HLA-DRB1 alleles and pemphigus vulgaris (PV) in a Han population in Sichuan.Methods Polymerase chain reaction with sequencespecific primer (PCR-SSP) method was used for low-resolution and high-resolution typing of HLA-DRB1 alleles in 19 patients of Han nationality with PV and 25 healthy controls in Sichuan.Allele frequencies were calculated,and differences in the allele frequency between the above two groups were compared by using chisquare test.Results Totally,9 kinds of DRB 1 low-resolution alleles and 19 kinds of DRB 1 high-resolution alleles were identified in the PV patients and healthy controls.Frequencies of the DRB1* 14 allele (39.47％[15/38] vs.8.00％[4/50],x2 =17.43,P ＜ 0.05) and DRB1*1405 allele (15.79％[6/38] vs.2.00％[1/50],x2 =4.25,P ＜ 0.05) were significantly higher in the PV patients than in the healthy controls.Conclusion The HLA-DRB1*14 allele may be a common susceptibility gene for PV in the Han population in Sichuan,and the HLA-DRB1* 1405 allele may be most closely associated with PV.

Human leukocyte antigen typing using buccal swabs as accurate and non-invasive substitute for venipuncture in children at risk for celiac disease.

BACKGROUND AND AIM: Human leukocyte antigen (HLA) typing is an important step in the diagnostic algorithm for celiac disease (CD) and is also used for screening purposes. Collection of blood is invasive and accompanied with emotional impact especially in children. Genetic technological progress now enables HLA typing from buccal cell samples. This study evaluated the reliability and feasibility of HLA typing for CD-associated HLA polymorphisms using buccal swabs as routine test in high-risk individuals. METHODS: Blood and buccal swabs of 77 children and adolescents with high risk for CD were prospectively collected in this cohort study. Buccal swab collection was performed either by the investigator at the outpatient clinic or by the patient or its parents at home. To evaluate the possibility of self-administration, three families performed the test at home. DNA was extracted using an adapted QIAamp method. Quantity, quality, and purity of DNA were recorded. HLA-DRB1, HLA-DQA1, and HLA-DQB1 typing was examined on buccal cell-derived and blood-derived DNA at low and, if necessary, high resolution level, using sequence-specific oligonucleotide and sequence-based typing, respectively. RESULTS: DNA isolation using buccal swabs yielded a good quality and sufficient quantity of DNA to perform HLA-DQ typing in all individuals. HLA typing results on buccal cell-derived DNA were identical to typing on blood-derived DNA, also for the self-administered samples. CONCLUSION: Introduction of the buccal swab test for HLA typing of CD risk in routine diagnostics can omit the current venipuncture and enables self-administration at home. Therefore, the buccal swab test is beneficial for individuals with a clinical suspicion for CD, as well as for screening purposes in high-risk populations.

The role of KIR2DL3/HLA-C*0802 in Brazilian patients with rheumatoid vasculitis

OBJECTIVES: Rheumatoid arthritis is a polygenically controlled systemic autoimmune disease. Rheumatoid vasculitis is an important extra-articular phenotype of rheumatoid arthritis that can result in deep cutaneous ulcers. The objective of this study was to establish a correlation between the frequency of major histocompatibility complex class I/II alleles and killer immunoglobulin-like receptor genotypes in patients with cutaneous rheumatoid vasculitis. METHODS: Using the Scott & Bacon 1984 criteria to diagnose rheumatoid vasculitis and after excluding any other causes such as diabetes, atherosclerosis, adverse drug reactions, infection, and smoking, patients who met the criteria were selected. All of the selected rheumatoid vasculitis patients presented deep cutaneous ulcers. Identification of the major histocompatibility complex class I/II and killer immunoglobulin-like receptor genotypes was performed by polymerase chain reaction assays of samples collected from the 23 rheumatoid vasculitis patients as well as from 80 controls (40 non-rheumatoid vasculitis RA control patients and 40 healthy volunteers). RESULTS: An association between the presence of the HLA-DRB1*1402 and HLA-DRB1*0101 alleles and cutaneous lesions in rheumatoid vasculitis patients and a correlation between the inhibitor KIR2DL3 and the HLA-C*0802 ligand in rheumatoid vasculitis patients were found. CONCLUSION: An association was found between the presence of the HLA-DRB1*1402 and HLA-DRB1*0101 alleles and the development of cutaneous lesions in rheumatoid vasculitis patients. Additionally, the HLA-C*0802 ligand protects these individuals from developing cutaneous lesions. .

Association of HLA-DRB1 with Sarcoidosis Susceptibility and Progression in African Americans.

HLA-DRB1 is a sarcoidosis risk gene, and the *03:01 allele is strongly associated with disease resolution in European sarcoidosis cases. Whereas the HLA-DRB1 variation is associated with sarcoidosis susceptibility in African Americans, DRB1 risk alleles are not as well defined, and associations with disease resolution have not been studied. Associations between genotyped and imputed HLA-DRB1 alleles and disease susceptibility/resolution were evaluated in a sample of 1,277 African-American patients with sarcoidosis and 1,467 control subjects. In silico binding assays were performed to assess the functional significance of the associated alleles. Increased disease susceptibility was associated with the HLA-DRB1 alleles *12:01 (odds ratio [OR], 2.11; 95% confidence interval [CI], 1.65-2.69; P = 3.2 × 10(-9)) and *11:01 (OR, 1.69; 95% CI, 1.42-2.01; P = 3.0 × 10(-9)). The strongest protective association was found with *03:01 (OR, 0.56; 95% CI, 0.44-0.73; P = 1.0 × 10(-5)). The African-derived allele *03:02 was associated with decreased risk of persistent radiographic disease (OR, 0.52; 95% CI, 0.37-0.72; P = 1.3 × 10(-4)), a finding consistent across the three component studies comprising the analytic sample. The DRB1*03:01 association with disease persistence was dependent upon local ancestry, with carriers of at least one European allele at DRB1 at a decreased risk of persistent disease (OR, 0.36; 95% CI, 0.14-0.94; P = 0.037). Results of in silico binding analyses showed that DRB1*03:01 consistently demonstrated the highest binding affinities for six bacterial peptides previously found in sarcoidosis granulomas, whereas *12:01 displayed the lowest binding affinities. This study has identified DRB1*03:01 and *03:02 as novel alleles associated with disease susceptibility and course in African Americans. Further investigation of DRB1*03 alleles may uncover immunologic factors that favor sarcoidosis protection and resolution among African Americans.

Association of HLA-DRB1 alleles and anti-neutrophil cytoplasmic antibodies in Han and Uyghur patients with ulcerative colitis in China.

OBJECTIVE: We aimed to study the association between HLA-DRB1 alleles and anti-neutrophil cytoplasmic antibodies (ANCA) among Uyghur and Han patients with ulcerative colitis (UC) in China. METHODS: Altogether 160 UC patients and 466 healthy controls of Uyghur and Han groups residing in the Xinjiang Uyghur Autonomous Region of China were included. HLA-DRB1 variants were identified from genomic DNA using polymerase chain reaction and gene sequencing. Serum ANCA were determined by indirect immunofluorescence assay. RESULTS: Among the Uyghur populations, the HLA-DRB1*08 gene frequency was lower in the UC patients than in the control group (P = 0.012, OR 0.12, 95% CI 0.02-0.91); however, that of HLA-DRB1*13 was much higher in the UC patients than in the controls (P = 0.001, OR 4.32, 95% CI 1.92-9.74). In Han patients with UC, there was no significant difference in HLA-DRB1 frequency between UC patients and healthy controls. The positive rate of ANCA in Uyghur patients with UC was significantly higher than in Han UC patients (P = 0.026), and ANCA positivity was associated with an increased frequency of HLA-DRB1*13 in Uyghur UC patients, but no such difference was observed in the Han patients. CONCLUSIONS: Genetic polymorphisms of the HLA-DRB1*08 and *13 may contribute to the clinical heterogeneity of UC between Uyghur and Han UC patients in China. In Uyghur UC patients, HLA-DRB1*13 may be correlated with ANCA positivity.

HLA frequencies and associations in cystic fibrosis.

Cystic fibrosis (CF) is classically attributed to the dysfunction of the single CF transmembrane conductance regulator gene. The incidence of human leukocyte antigen (HLA) polymorphisms in different CF-associated diseases raises the question of an unequal distribution of HLA genotypes in CF. This study aimed to evaluate HLA gene frequencies and possible associations in CF patients compared with a control population. Frequencies of HLA-DRB1, HLA-DQA1 and HLA-DQB1, performed by intermediate resolution typing using Luminex sequence-specific oligonucleotide, and epitope counts were similar in 340 CF patients when compared with 400 control subjects. In conclusion, HLA-DRB1, -DQA1 and -DQB1 do not seem to influence susceptibility to CF. Whether HLA plays a role in the severity of CF disease needs to be investigated.

Interaction between HLA-DRB1 gene polymorphism and environmental risk factors in the development of gestational diabetes mellitus / 中华妇产科杂志

Objective To explore the interactions between human leukocyte antigen ( HLA)-DRB1 gene polymorphism and environmental risk factors in gestational diabetes mellitus ( GDM ) pathogenesis.Methods Pregnant women who had prenatal cares in Obstetric Department , West China Second Hospital of Sichuan University were recruited from January 1st to December 31st in 2011.A prospective cohort study was conducted in the women who had a glucose challenge test ( GCT) or 75 g oral glucose tolerance test ( OGTT) during 24-28 gestational weeks.A total of 104 women diagnosed with GDM were randomly included in GDM group while another 103 normal women fell into the control group.The HLA-DRB1 polymorphism was detected by Polymerase Chain Reaction -Sequence Specific Primers ( PCR-SSP) method in both groups.The interactions between HLA-DRB1 polymorphism and environmental risk factors were analyzed based on the simple-case-study method.Results ( 1 ) There were 712 pregnant women with complete perinatal information during January 1st to December 31st, 2011, among whom 175 (24.6%) women were diagnosed with GDM.A logistic regression analysis showed that advanced maternal age (OR=1.081, 95%CI:1.027-1.138), imbalanced diet (OR=3.329, 95%CI:2.167 -5.116), high body mass index (BMI≥24.0 kg/m2) before pregnancy (OR=1.095, 95%CI:1.008 -1.190), HBsAg carrier status (OR=3.173, 95%CI:1.387-7.260) and family history of diabetes mellitus (DM) (OR=1.798, 95%CI:1.063 -3.041) were risk factors of GDM.(2) There were 49 HLA-DRB1 genotypes and 51 HLA-DRB1 genotypes in GDM group and the control group , respectively.We further compared the genotypes that occurred in over 3 cases in either group and found that HLA-DRB1*12,16 was only detected in 5 cases (5/103, 4.9%) in control group,and the difference was significant between the two groups (P=0.029).HLA-DRB1*11,16 and HLA-DRB1*09,09 were only detected in 4 cases (3.8%,4/104) and 5 cases (4.8%, 5/104) in GDM group respectively , but without significant differences between the two groups ( P >0.05 ).No significant difference was found in other genotype frequencies between the two groups ( P>0.05 ).( 3 ) Thirteen types of HLA-DRB1 allele were detected but no significant differences were observed in their frequencies between two groups ( P>0.05).(4) A positive interaction was detected between HLA-DRB1*07 polymorphism and advanced maternal ages (OR=5.952, 95%CI:1.314-26.970, P=0.022), while no interaction was found between HLA-DRB polymorphisms to other risk factors such as imbalanced diet , high body mass index ( BMI≥24.0 kg/m2 ) , HBsAg carrier status or DM family history.Conclusions Advanced maternal age, unbalanced diet, high body mass index (BMI≥24.0 kg/m2), HBsAg carrier status and DM family history are environmental risk factors of GDM in Chengdu.While HLA-DRB1*12,16 genotype may be a protective genotype for GDM.There is a positive interaction between HLA-DRB1*07 polymorphism and advanced maternal age which may play a critic role in GDM development.

The correlation between human leukocyte antigen-DRB1 alleles and anti-neutrophil cytoplasmatic antibodies in Han and Uygur ulcerative colitis patients in Xinjiang region / 中华消化杂志

Objective To study the correlation between human leukocyte antigen (HLA)-DRB1 alleles and anti neutrophil cytoplasmatic antibodies (ANCA) in Han and Uygur ulcerative colitis (UC)patients in Xinjiang region.Methods The serum ANCA was determined by indirect immunofluorescence assay in 62 Uygur UC patients,58 Han UC patients,188 Uygur and 184 Han healthy control individuals.HLA-DRB1 typing was performed by polymerase chain reaction-sequence based typing (PCR-SBT).The allele frequency of HLA-DRB1 was compared in ANCA positive and negative Han and Uygur patients as well as healthy controls.Stratified analysis was performed according to UC clinical type,severity and involvement.SPSS 17.0 software was applied for x2 test.Once P＜0.05,the odds ratio (OR) and 95％ confidence intervals (95％CI) was calculated.Results The positive rate of ANCA in Uygur UC patients (53.2％,33/62) was significantly higher than that of Han patients (34.5％,20/58) and the difference was statistically significant (x2=4.269,P =0.045).In Uygur,the gene frequency of HLA-DRB1 * 13 in ANCA positive UC patients (0.202)was significantly higher than that of ANCA negative patients (0.017) (x2 =10.092,P=0.016,OR=16.000,95％CI:2.892 to 88.524) and healthy controls (0.075) (x2=9.351,P＝0.040,OR=3.407,95％CI:1.666 to 6.971).The gene frequency of HLA-DRB1 * 13 in ANCA positive pancolitis type UC patients (9/15) was significantly higher than that of ANCA negative pancolitis type UC patients (1/14) and the difference was statistically significant (x2=8.955,P =0.040,OR =19.500,95％CI:2.787 to 136.461).However,in Han patients,there were no significant differences of HLA-DRB1 alleles frequencies among ANCA positive patients,ANCA negative patients and healthy controls (all P＞0.05),and the results of stratified analysis were same.Conclusions In Uygur UC patients of Xinjiang region,HLA-DRB1 * 13 may correlated with ANCA and with ANCA of pancolitis type UC patients.There is no such correlation in Han patients of Xinjiang region.