Causal relationships between autoimmune diseases and celiac disease: A Mendelian randomization analysis.

The aim of this study was to investigate the causal relationship between autoimmune disorders and celiac disease (CeD) through Mendelian randomization (MR). Single nucleotide polymorphisms (SNPs) significantly associated with 13 autoimmune diseases were extracted from the summary statistics of European genome-wide association studies (GWAS), and their effects were examined by Inverse variance-weighted (IVW) in a large European GWAS on CeD. Finally, reverse MR was performed to investigate the causal effects of CeD on autoimmune traits. Following the application of Bonferroni correction for multiple testing, genetically determined seven autoimmune diseases are causally associated with CeD: Crohn's disease (CD) (OR [95%CI] = 1.156 [1.106 ± 1.208], P = 1.27E-10), primary biliary cholangitis (PBC) (1.229 [1.143 ± 1.321], P = 2.53E-08), primary sclerosing cholangitis (PSC) (1.688 [1.466 ± 1.944], P = 3.56E-13), rheumatoid arthritis (RA) (1.231 [1.154 ± 1.313], P = 2.74E-10), systemic lupus erythematosus (SLE) (1.127 [1.081 ± 1.176], P = 2.59E-08), type 1 diabetes (T1D) (1.41 [1.238 ± 1.606], P = 2.24E-07), and asthma (1.414 [1.137 ± 1.758], P = 1.86E-03). The IVW analysis indicated that CeD increased the risk for seven diseases: CD (1.078 [1.044 ± 1.113], P = 3.71E-06), Graves' disease (GD) (1.251 [1.127 ± 1.387], P = 2.34E-05), PSC (1.304 [1.227 ± 1.386], P = 8.56E-18), psoriasis (PsO) (1.12 [1.062 ± 1.182], P = 3.38E-05), SLE (1.301[1.22 ± 1.388], P = 1.25E-15), T1D (1.3[1.228 ± 1.376], P = 1.57E-19), and asthma (1.045 [1.024 ± 1.067], P = 1.82E-05). The sensitivity analyses deemed the results reliable without pleiotropy. There are positive genetic correlations between various autoimmune diseases and CeD, and the latter also affects the predisposition to multiple autoimmune disorders in the European population.

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.

Difference in DRB1* gene polymorphisms between Han and Uyghur ulcerative colitis patients in China.

AIM: To evaluate the association between HLA-DRB1 alleles and Han and Uyghur ulcerative colitis (UC) patients residing in the Xinjiang Uyghur Autonomous Region of China. METHODS: In this study, 102 UC patients (53 Han including 22 men and 31 women, and 49 Uyghur patients including 25 men and 24 women; aged 48.07 ± 15.83 years) and 310 age- and sex-matched healthy controls were enrolled in the Department of Gastroenterology, Xinjiang People's Hospital of China from January 2010 to May 2011. UC was diagnosed based on the clinical, endoscopic and histological findings following Lennard-Jones criteria. Blood samples were collected and genomic DNA was extracted by routine laboratory methods, and both polymerase chain reaction and gene sequencing were used to identify HLA-DRB1 allele variants. The potential association between genetic variation and UC in Han and Uyghur patients was examined. There were no statistical differences in HLA-DRB1 allele frequencies in Han UC patients. RESULTS: There was no significant difference in the sex ratio between the controls and UC patients (P = 0.740). In Han patients with UC (n = 53), HLA-DRB1 *03, *13 allele frequencies were lower than in healthy controls (n = 161), but not statistically significant, and HLA-DRB1*04*11*14 allele frequencies were higher than in healthy controls, but without statistical significance. Differences between Uyghur UC patients and the control group were observed for HLA-DRB1*04 and HLA-DRB1*13, both showed a greater frequency in UC patients (10.21% vs 2.69%, P = 0.043; 14.29% vs 4.03%, P = 0.019). HLA-DRB1*14 also showed a greater frequency in UC patients (14.29% vs 2.69%, P = 0.006). The frequencies of DRB1*04, *13*14 alleles were increased in Uyghur UC patients compared with normal controls. The frequency of DRB1 * 08 was decreased in Uyghur UC patients compared with normal controls. HLA-DRB1 alleles showed no association with UC in Han patients. There were no statistical differences in HLA-DRB1 allele frequencies in Han UC patients. The frequencies of DRB1*04, *13*14 alleles were increased in Uyghur UC patients compared with normal controls. The frequency of DRB1*08 was decreased in Uyghur UC patients compared with normal controls. Polymorphism of the HLA-DRB1 gene may contribute to the clinical heterogeneity of UC between Han and Uyghur UC patients in China. CONCLUSION: HLA-DRB1*04*13*14 and DRB1*08 may contribute to the clinical heterogeneity of UC between Han and Uyghur UC patients.