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The objective of this study was to systemically and comprehensively evaluate the associations between smoking and disease outcomes in patients with ankylosing spondylitis (AS). Information on smoking, clinical features, and sociodemographic characteristics was collected by a questionnaire administered directly to the patient. Group differences were analyzed by t test or chi-square test. Logistic regression analysis was conducted with the Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), C-reactive protein, and erythrocyte sedimentation rate as the dependent variables and different stratification of smoking duration, smoking intensity, and cumulative smoking as independent variables. In order to compare our results with previous studies, meta-analysis was performed to calculate standardized mean difference (SMD) for relationship between outcomes and smoking status. A total of 1178 AS patients were analyzed. Compared with non-smokers, the risk of having active disease (BASDAI ≥ 4) was higher in patients who smoked at least 15 years, or 15 cigarettes per day, or 15 pack-years (OR = 1.70 [1.06, 2.73], 1.75 [1.08, 2.82], and 1.97 [1.06, 3.67], respectively); and smokers had increasing risk of BASDAI ≥ 4 with increasing years of smoking, or cigarettes per day, or pack-years (p-trend = 0.010, 0.008 and 0.006, respectively). The risk of having active disease was higher in patients who smoked at least 15 cigarettes per day or 15 pack-years (OR = 1.74 [1.06, 2.84] and 2.89 [1.56, 5.35], respectively), with increasing number of cigarettes per day and pack-years. Smokers had an increased risk of BASFI ≥ 4 (p-trend = 0.040 and 0.007, respectively). By meta-analysis, current, former and ever smokers had significantly higher BASDAI (SMD = 0.34 [0.18, 0.48], 0.10 [0.01, 0.19], and 0.27 [0.20, 0.34], respectively) and BASFI (SMD = 0.35 [0.16, 0.55], 0.30 [0.22, 0.39], and 0.35 [0.21, 0.50], respectively) compared to non-smokers. Smoking is a risk factor for greater disease activity and worse functioning in AS patients.

// Hui Zhang 1, * , Jing Liu 1, * , Zheng Dong 1, * , Yue Ding 2 , Qiaoxia Qian 2 , Jingru Zhou 2 , Yanyun Ma 2 , Zhendong Mei 1 , Xiangxiang Chen 1 , Yuan Li 1 , Ziyu Yuan 3 , Juan Zhang 3 , Yajun Yang 2, 3 , Xingdong Chen 1, 3 , Li Jin 1, 3 , Hejian Zou 4, 5 , Xiaofeng Wang 1, 3 and Jiucun Wang 1, 3, 5 1 State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China 2 Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China 3 Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China 4 Division of Rheumatology, Huashan Hospital, Fudan University, Shanghai, China 5 Institute of Rheumatology, Immunology and Allergy, Fudan University, Shanghai, China * These authors contributed equally to this work Correspondence to: Jiucun Wang, email: jcwang@fudan.edu.cn Xiaofeng Wang, email: xiaofengwang@fudan.edu.cn Keywords: serum urate, total bilirubin, mendelian randomization study Received: August 29, 2016 Accepted: October 03, 2017 Published: October 24, 2017 ABSTRACT Aim: A Mendelian randomization study (MRS) can be linked to a “natural” randomized controlled trial in order to avoid potential bias of observational epidemiology. We aimed to study the possible association between serum urate (SU) and total bilirubin (TBIL) using MRS. Materials and Methods: An observational epidemiological study using ordinary least squares (OLS) regression and MRS using two-stage least square (TLS) regression was conducted to assess the effect of SU on TBIL. The comparison between the OLS regression and the TLS regression was analyzed by the Durbin-Hausman test. If the p value is significant, it suggests that the OLS regression cannot evaluate the relationship between exposure and outcome, and the TLS regression is precise; while if the p value is not significant, there would be no significant difference between the two regressions. Results: A total of 3,753 subjects were analyzed. In OLS regression, there was no significant association between SU and TBIL in all subjects and subgroup analysis (all p > 0.05). However, MRS revealed a negative correlation between SU and TBIL after adjustment for confounders (beta = –0.021, p = 0.010). Further analysis was conducted in different SU subgroups, and results show that elevated SU was associated with a significant reduction in TBIL after adjustment for hyperuricemic subjects (beta = –0.053, p = 0.027). In addition, the results using the Durbin-Hausman test further confirmed a negative effect of SU on TBIL ( p = 0.002 and 0.010, respectively). Conclusions: This research shows for the first time that elevated SU was a potential causal factor in the reduction of TBIL and it provides strong evidence to resolve the controversial association between SU and TBIL.

The study aimed to determine whether unique clinical patterns of AS may exist in China, specifically to explore the different clinical manifestations caused by gender, HLA-B27 status, and age at disease onset. The multicenter cross-sectional survey was conducted and 1251 patients were enrolled across China, representing a broad spectrum of Chinese AS patients. The mean age at onset and diagnosis were 29.2 (11.4) and 33.5 (12.6) years, respectively. The male/female ratio was 2.7:1. Acute anterior uveitis (AAU) was experienced in 10.3% of AS patients and 9.1% patients had juvenile-onset AS (JoAS). Men were significantly younger at onset and diagnosis and showed a higher frequency of HLA-B27 positivity, JoAS, and AAU than women. HLA-B27-positive patients had a younger age of onset than HLA-B27-negative patients. HLA-B27-positive patients were nearly three times as likely to develop AAU than negative patients (P = 0.04). JoAS patients had a family history of AS more often than adult-onset AS (AoAS) patients, and 4.9% of JoAS patients underwent surgical treatments, a rate more than six times that of AoAS patients (P = 0.01). Men had higher levels of C-reactive protein than women, as did HLA-B27 positives compared to negative patients, and JoAS compared to AoAS (all P

High levels of serum uric acid can predict the progression of stage I and II chronic kidney disease (CKD), but whether serum urate is an independent risk factor or has causal impact on serum creatinine (SCr) and renal function remains unclear. Mendelian randomization was used to determine whether serum uric acid had a causal effect on renal function, represented by estimated glomerular filtration rate (eGFR), with potential confounding factors, in 3734 subjects from the Taizhou Longitudinal Study. In the two-stage least squares method of Mendelian randomization, serum uric acid level was selected as the exposure, genetic risk score of uric acid transporters was selected as the instrumental variable, and SCr and eGFR were selected as the outcomes. The result of the analysis showed that increased serum uric acid was not a causal effect on renal function, but it was a causal effect on reducing estimated glomerular filtration rate in both the female population and the subjects who were under 65 years old. We also found that increased serum uric acid levels led to impaired renal function only in the subjects with normal eGFR values. In addition, the serum uric acid was a risk factor for renal function in the subjects with relatively high levels of fasting glucose or who were currently smokers. Although serum urate is not an independent risk factor for renal dysfunction, it has a causal effect on renal dysfunction in either female or individuals of under 65, or normal eGFR, or high level of fasting glucose, or current smokers.

Gout is a common inflammation disease resulting from an increase in serum uric acid. Nearly 70% of uric acid is excreted via the kidneys. To date, evidence for an association between genetic loci and gout is absent, equivocal or not replicated. Our study aims to test variants in two genes abundantly expressed in the kidney, LRP2 and COMT, for their association with uric acid and gout. In total, 1318 Chinese individuals were genotyped for rs2544390 in LRP2 and rs4680 in COMT. These LRP2 and COMT gene polymorphisms showed no significant effect on uric acid (P = 0.204 and 0.188, separately); however, rs2544390 in LRP2 did influence uric acid levels in individuals with BMI ≥ 25 (P = 0.009). In addition, the allele frequency distributions of the two loci showed a significant difference between gout patients and healthy controls. A missense variation in rs4680 (G > A) decreased the risk of gout (OR = 0.77, P = 0.015), whereas the T allele of rs2544390 was associated with gout pathogenesis risk (OR = 1.26, P = 0.020). The present study provides the first evidence for an association between COMT and gout. Rs2544390 in LRP2 only influenced uric acid levels in individuals with BMI ≥ 25, which might explain the discrepant results among previous studies. In addition, we are the first to identify the association between LRP2 and gout in a Chinese population and to confirm this association in Asians.