ABSTRACT
BACKGROUND AND OBJECTIVES: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by humoral autoimmunity. The etiology of SLE is thought to be multifactorial including environmental, hormonal, and genetic factors. The human leukocyte antigen (HLA) has extensively been associated with the susceptibility to SLE; however, the association is heterogeneous among different ethnic groups. The aim of this study was to determine the association of HLA-A, HLA-B, HLA-DRB1, and HLA-DQB1 with SLE susceptibility in the Saudi population. DESIGN AND SETTINGS: A total of 86 consecutive SLE patients attending the rheumatology clinic at King Abdulaziz Medical City, Riyadh, were recruited for this study. METHODS: HLA types were determined by the polymerase chain reaction sequence-specific oligonucleotide (PCR-SSP) method in 86 patients and 356 control subjects. RESULTS: The following HLA alleles were found to be positively associated with SLE: HLA-A*29 (OR=2.70; 95% CI=1.03-7.08; P=.0035), HLA-B*51 (OR=1.81; 95% CI=1.17-2.79; P=.0066), HLA-DRB1*15 (OR=1.45; 95% CI=0.98-2.29; P=.063), and HLA-DQB1*06 (OR=1.67; 95% CI=1.19-2.36; P=.0032), whereas HLA-DRB1*16 was negatively associated with the disease (OR=0.18; 95% CI=0.02-1.3; P=.055). HLA-DRB1*15 haplotypes were significantly associated with SLE (OR=2.01, 95% CI=1.20-3.68, P=.008); this was mainly due to the HLADRB1*15-DQB1*06 association. CONCLUSIONS: Our data suggest an association between MHC class I and class II (HLA-A*29, HLA-B*51, HLA-DRB1*15, and HLA-DQB1*06) and susceptibility to SLE in the Saudi population. HLA-DRB1*15-DQB1*06 haplotype showed the highest risk factor for the disease that is similar to what was seen in the African American patients, suggesting shared susceptibility genetic factors among these ethnic groups.
Subject(s)
Genetic Predisposition to Disease , HLA-DQ beta-Chains/genetics , HLA-DRB1 Chains/genetics , Lupus Erythematosus, Systemic/genetics , Adolescent , Adult , Alleles , Case-Control Studies , Child , Female , Genes, MHC Class I/genetics , Genes, MHC Class II/genetics , Haplotypes , Humans , Male , Middle Aged , Polymerase Chain Reaction , Risk Factors , Saudi Arabia , Young AdultABSTRACT
BACKGROUND: Association of NOD2 (CARD15) gene mutations with inflammatory bowel diseases (IBD) is well known. We herein aimed to investigate the role of familial Mediterranean fever-associated MEFV variations in IBD patients as additional regional-specific risk factor. STUDY: One hundred thirty-seven (78 female, 56.9%) IBD patients [62 Crohn's disease (CD), 75 ulcerative colitis (UC)] were enrolled into the study. The diagnosis of all patients was confirmed by colonoscopy, histopathology, and the clinical findings. One hundred one healthy donors' samples were used as healthy controls. All patients were genotyped for the most common E148Q, M608I, M694V, and V726A variations of the MEFV and R702W, G908R, and 1007fs of the NOD2. RESULTS: The overall MEFV variation frequency was found to be higher in the IBD (25.5%) patients (28% in UC, 22.6% in CD) compared with controls (9.9%, P=0.006). This association was stronger with the penetrant exon 10 variations (M694V, M680I, V726A; odds ratio =4.5, P=0.001). Contribution of M694V was higher compared with the other variations (14.5% in CD, 17.3% in UC and 3% in controls, odds ratio =6.039, 95% confidence intervals, 1.7-20.7, P=0.002). The overall frequency of 3 NOD2 variants in the IBD group was not different from that of controls. CONCLUSIONS: The results of this study suggest that the MEFV variations may be an additional susceptibility factor for IBD in certain parts of the world where the carrier rate is high, and the genetic background of the IBD patients may show regional changes.
