We performed a genome-wide association study (GWAS) of systemic lupus erythematosus (SLE) in a Chinese Han population by genotyping 1,047 cases and 1,205 controls using Illumina Human610-Quad BeadChips and replicating 78 SNPs in two additional cohorts (3,152 cases and 7,050 controls). We identified nine new susceptibility loci (ETS1, IKZF1, RASGRP3, SLC15A4, TNIP1, 7q11.23, 10q11.22, 11q23.3 and 16p11.2; 1.77 x 10(-25) < or = P(combined) < or = 2.77 x 10(-8)) and confirmed seven previously reported loci (BLK, IRF5, STAT4, TNFAIP3, TNFSF4, 6q21 and 22q11.21; 5.17 x 10(-42) < or = P(combined) < or = 5.18 x 10(-12)). Comparison with previous GWAS findings highlighted the genetic heterogeneity of SLE susceptibility between Chinese Han and European populations. This study not only advances our understanding of the genetic basis of SLE but also highlights the value of performing GWAS in diverse ancestral populations.

To identify susceptibility loci for ankylosing spondylitis, we performed a two-stage genome-wide association study in Han Chinese. In the discovery stage, we analyzed 1,356,350 autosomal SNPs in 1,837 individuals with ankylosing spondylitis and 4,231 controls; in the validation stage, we analyzed 30 suggestive SNPs in an additional 2,100 affected individuals and 3,496 controls. We identified two new susceptibility loci between EDIL3 and HAPLN1 at 5q14.3 (rs4552569; P = 8.77 × 10(-10)) and within ANO6 at 12q12 (rs17095830; P = 1.63 × 10(-8)). We also confirmed previously reported associations in Europeans within the major histocompatibility complex (MHC) region (top SNP, rs13202464; P < 5 × 10(-324)) and at 2p15 (rs10865331; P = 1.98 × 10(-8)). We show that rs13202464 within the MHC region mainly represents the risk effect of HLA-B*27 variants (including HLA-B*2704, HLA-B*2705 and HLA-B*2715) in Chinese. The two newly discovered loci implicate genes related to bone formation and cartilage development, suggesting their potential involvement in the etiology of ankylosing spondylitis.

A series of 2-(2-nitrobenzoyl)cyclohexane-1,3-dione analogues (1-9) were designed, synthesized, and evaluated for inhibition of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD), a key enzyme involved in the catabolism of tyrosine which catalyzes the conversion of 4-hydroxyphenylpyruvate to homogentisate. The correlations between the results of enzyme inhibition, ferric chloride tests, and the conformational analysis suggested that the tight binding between triketone-type inhibitors and 4-HPPD is likely due to chelation of the enzyme-bound ferric iron with the enol tautomer of 1,3-diketone moiety of the triketones. The presence of a 2-carbonyl group in the triketone is an essential structural feature for potent 4-HPPD inhibition. Modification of the 3-carbonyl group of triketone moiety to other functionality will reduce the overall planarity and thus prevent keto-enol tautomerization, resulting in a decrease or lack of inhibition activity.

There are reports of IL-1 complex gene polymorphisms in ankylosing spondylitis (AS; MIM 106300), but the results have been inconsistent among populations. Moreover, few studies examine the association between IL-1 complex gene polymorphisms and clinical symptoms of AS patients. We investigated polymorphisms of IL-1 complex with AS in the Chinese Han population in this study. Chinese Han AS patients and ethnically matched healthy controls were genotyped for five single nucleotide polymorphisms (IL1beta+3953, beta-511, F10.3, RN.4, RN.6/1) and the IL1RN.VNTR of IL-1 gene cluster. Allele, Genotype and haplotype frequencies were compared between cases and controls by SHEsis software. The frequency of allele C of the marker IL1F10.3 was significantly increased in AS patients versus controls [p = 0.001, odds ratio (OR) = 1.54, 95% confidence interval (CI) = 1.19-1.20; p = 0.002, respectively]. Strong linkage disequilibrium was identified between IL1B-511, IL1B+3953 and RN4 in both patients and healthy controls (D' > 0.95). Haplotypes of pairs of these markers (6) were also significantly associated with AS. The strongest associations observed was between allele combination B-511-T/B+3953-C/F10.3-C/RN4-T/RN2VNTR-1/RN6.1-C and AS (p = 3.32 x 10(-5), OR = 4.41, 95% CI=2.1-9.3). Clinical manifestation showed week association between RN2VNTR A2 allele and risk of peripheral arthritis (OR = 0.2, 95% CI = 0.07-0.91). The IL-1 gene cluster is associated with AS in Chinese population. This finding provides strong statistical support for the previously observed relationship and indicates possible association between clinical manifestation and genetic factor.

Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is a standard instrument regularly used to assess disease activity of patients with ankylosing spondylitis (AS). However, the well-being of a patient is also affected by impairment of function as well as psychological status and other factors. The objective of this study was to evaluate if psychological status, stressful life events, and sleep quality contribute significantly to BASDAI. Six hundred eighty-three AS patients satisfying the Modified New York Criteria for AS were recruited from the rheumatology clinics of seven hospitals in China. Patients with other concomitant disorders were excluded. Participants were requested to complete a set of clinical examinations and the following questionnaires: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Zung Self-Rating Anxiety Scale (SAS), Zung Self-Rating Depression Scale (SDS), Pittsburgh Sleep Quality Index Questionnaire (PSQI), Health Assessment Questionnaire for Spondyloarthropathies (HAQ-S), and Social Readjustment Rating Scale (SRRS). Spearman correlation analysis showed that BASDAI was highly associated with degree and duration of morning stiffness, overall pain, nocturnal back pain, overall back pain, anxiety, and BASFI (all P < 0.001), but were not associated with education, HAQ-S, and sleep medication in PSQI (P > 0.05). Multiple stepwise regression analysis indicated that overall pain was the maximal statistical contribution in predicting disease activity (standardized coefficient, 0.335). In hierarchic multiple regression analysis, psychological variables added an only additional 2.7% to the overall R(2) beyond that accounted for by demographic and medical variables, resulting in a final R(2) of 53.5%. Although BASDAI is a very good measurement of pain and stiffness and to a certain extent effect of functional impairment in AS, it barely takes into account psychological status, stress life events, and sleep quality These factors should be evaluated by other modalities.