Assessment of the Association between Genetic Polymorphisms in the CHI3L1 Gene and Asthma Risk.

BACKGROUND: Chitinase 3-like 1 (CHI3L1) is an important factor involved in the development of asthma. This meta-analysis assessed the association of the CHI3L1 polymorphisms rs4950928, rs10399931, rs883125, rs880633, and rs10399805 with asthma risk. METHODS: The literature searches were conducted in PubMed, Web of Science, Wanfang, and China National Knowledge Infrastructure up until September 4, 2021, for relevant studies. Sixteen publications with 18 studies involving 5,005 asthma patients and 9,725 controls were included in this meta-analysis. RESULTS: The meta-analyses showed that among East-Asian subjects, increased asthma risk was associated with CHI3L1 rs4950928 (GG + CG vs. CC: odds ratio [OR] = 1.43, 95% confidence interval [CI]: 1.09-1.88, p = 0.011; GG vs. CG + CC: OR = 1.64, 95% CI: 1.20-2.26, p = 0.002; GG vs. CC: OR = 1.97, 95% CI: 1.41-2.75, p = 0.000; and G vs. C: OR = 1.36, 95% CI: 1.12-1.66, p = 0.002) and rs883125 (G vs. C: OR = 1.42, 95% CI: 1.01-1.99, p = 0.043), whereas CHI3L1 rs10399931 was associated with reduced asthma risk (TT vs. CT + CC: OR = 0.79, 95% CI: 0.64-0.99, p = 0.038; TT vs. CC: OR = 0.77, 95% CI: 0.61-0.98, p = 0.030). In addition, we found an association between CHI3L1 rs4950928 and asthma risk in adult subjects but not children, while CHI3L1 rs883125 was associated with asthma risk in children. CONCLUSION: The CHI3L1 polymorphisms rs4950928, rs10399931, and rs883125 are important genetic factors for asthma among East-Asian subjects.

Single nucleotide polymorphisms of IL-13 and CD14 genes in allergic rhinitis: a meta-analysis.

PURPOSE: The aim of this study was to conduct a meta-analysis for single nucleotide polymorphisms (SNPs) in interleukin-13 (IL-13) and cluster of differentiation 14 (CD14) genes and the risk for allergic rhinitis (AR). METHODS: We screened studies identified through seven databases including Pubmed, Medline, Web of Science, Embase, China Biology Medicine disc, Wanfang, and China Academic Journal Network Publishing Database. The odds ratios (ORs) and 95% confidence intervals (CIs) were determined to assess the association under allelic, dominant and recessive models. RESULTS: Twelve studies with a total of 8547 participants (3223 cases and 5324 controls) investigated IL-13 SNP rs20541, five studies combining 4580 participants (1411 cases and 3169 controls) examined IL-13 SNP rs1800925, and nine studies with 2301 participants (1174 cases and 1127 controls) assessed CD14 SNP rs2569190. We found that the A allele of IL-13 SNP rs20541 was associated with an increased risk of AR (OR 1.19, 95% CI 1.11-1.28, P < 0.001). Stratifying studies by ethnic group produced significant results in Asians (OR 1.21, 95% CI 1.11-1.32, P < 0.001), but not in Caucasians (OR 1.14, 95% CI 1.00-1.30, P = 0.051). No association of IL-13 SNP rs1800925 and CD14 SNP rs2569190 with AR risk was found in either Asians or Caucasians (P > 0.05). CONCLUSION: Our findings suggest that IL-13 SNP rs20541 is significantly associated with AR risk in Asians but not in Caucasians. However, the accumulating evidence does not support an association of IL-13 SNP rs1800925 and CD14 SNP rs2569190 with AR risk.

Lack of Association Between the IL1B (-511 and +3954), IL1RN VNTR Polymorphisms and Tuberculosis Risk: A Meta-analysis.

BACKGROUND: Several recent studies have provided evidence that polymorphisms in the interleukin-1 (IL1) gene are implicated in tuberculosis (TB). However, results of different studies are inconsistent. The aim of this study was to perform a meta-analysis investigating the association of the IL1B (-511 and +3954) and IL1RN VNTR polymorphisms with TB risk. METHODS: A systematic review of the English literature was conducted by searching Pubmed, Scopus, and ISI Web of Knowledge databases for relevant studies. Pooled odds ratios (OR) with 95 % confidence intervals (CI) were calculated using fixed effects models. Between-study heterogeneity and publication bias were also evaluated. RESULTS: Nine case-control studies including 3327 participants were reviewed and analyzed. Our results did not indicate any association of the IL1B (-511 and +3954) and IL1RN VNTR polymorphisms with TB risk in the overall populations. The pooled OR of the IL1B -511 polymorphism was 1.09 (95 % CI 0.87-1.36) for the dominant model, 1.11 (0.89-1.38) for the recessive model, 1.15 (0.87-1.50) for the homozygote model, and 1.07 (0.94-1.23) for the allelic comparison model. ORs for the IL1B +3954 and IL1RN VNTR polymorphisms were similar. In subgroup analysis stratified by ethnicity, the results revealed no association between these polymorphisms and TB risk in black people, Asians, and Caucasians, respectively. We did not identify significant between-study heterogeneity across all studies, and there was no evidence of publication bias. CONCLUSIONS: Our results indicate there is a lack of association between the IL1B (-511 and +3954), IL1RN VNTR polymorphisms and TB risk.

Association of the MMP-3, MMP-9 and MMP-12 gene polymorphisms with COPD risk: a meta-analysis.

Introduction: Given the evidence that the matrix metalloproteinases (MMPs) play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD), a number of case-control studies have attempted to assess the relationship between genetic polymorphisms in MMP genes and COPD risk. However, reliable measures of these results are lacking. Material and methods: We assessed the published evidence for association of the MMP-3, MMP-9 and MMP-12 polymorphisms with COPD risk using meta-analytic techniques. The odds ratio (OR) and 95% confidence interval (CI) were calculated for each study using fixed or random effect models. Results: A total of 23 case-control studies were included in the meta-analysis. No significant association was observed between the MMP-9 rs3918242 polymorphism and COPD risk in the overall populations under the dominant (T/T + C/T vs. C/C: OR = 1.30, 95% CI: 1.00-1.69, p = 0.054) and allele contrast (T allele vs. C allele: OR = 1.22, 95% CI: 0.97-1.53, p = 0.088) models. However, in sub-group analysis the polymorphism rs3918242 was significant in Asians under the dominant model (T/T + C/T vs. C/C: OR = 1.66, 95% CI: 1.02-2.72, p = 0.043). The results for MMP-12 rs2276109 showed an association with COPD only in mixed populations (G/G + A/G vs. A/A: OR = 1.57, 95% CI: 1.10-2.24, p = 0.013; G allele vs. A allele: OR = 1.52, 95% CI: 1.09-2.14, p = 0.015). We did not find any significant association of the MMP-12 rs652438 and MMP-3 rs35068180 polymorphisms with COPD. Conclusions: The findings of this meta-analysis suggest that there is a risk of COPD associated with the MMP-9 rs3918242 and MMP-12 rs2276109 polymorphisms in certain ethnic groups.

[Changes of CD(4)(+)Foxp3(+) regulatory T cells and CD(4)(+)IL-17(+)T cells in cigarette smoke-exposed rats].

OBJECTIVE: To evaluate the changes of CD(4)(+)IL-17(+) T (Th17) and CD(4)(+)Foxp3(+) regulatory T (Treg) cells in peripheral blood and bronchoalveolar lavage fluid (BALF), and therefore to explore the role of Th17 and Treg in cigarette smoke-induced airway inflammation/COPD in rats. METHODS: Forty male Wistar rats were randomly divided into 4 groups: a 12 wk smoke-exposure group, a 24 wk smoke-exposure group, a 12 wk control group and a 24 wk control group (n = 10 each). Cells in BALF were collected and analyzed by absolute and differential cell counts. IL-17 and IL-6 levels in serum and BALF were tested by enzyme linked immunosorbent assay (ELISA). The proportion of CD(4)(+)IL-17(+) T and CD(4)(+)Foxp3(+) Treg in peripheral blood and BALF were determined by flow cytometry. The mRNA expressions of IL-17 and Foxp3 were measured by real-time PCR. Comparisons of the data between different groups were performed using one-way ANOVA, and SNK and Games-Howell test were used for comparison between 2 groups. RESULTS: Levels of IL-17 were remarkable increased in the 12 wk smoke-exposure group and the 24 wk smoke-exposure group in serum [(52.6 ± 1.8) ng/L, (75.4 ± 6.0) ng/L] and BALF [(78.1 ± 5.8) ng/L, (95.0 ± 6.8) ng/L] compared with the 12 wk control group [(40.0 ± 3.2)ng/L, (54.5 ± 4.6) ng/L] and the 24 wk control group [(36.7 ± 3.2) ng/L, (53.9 ± 3.7) ng/L], all P < 0.05. IL-6 in serum was significantly increased in the 24 wk smoke-exposure group [(31.4 ± 2.1) ng/L] compared with the 24 wk control group [(11.5 ± 0.5) ng/L], and it was increased in the 12 wk and the 24 wk smoke-exposure group [(33.3 ± 2.3) ng/L, (44.6 ± 3.0) ng/L] compared with the 12 wk and the 24 wk control group [(15.6 ± 1.8) ng/L, (18.0 ± 1.9) ng/L] in BALF. Ratio of Th17 was higher in the 12 wk and the 24 wk smoke-exposure groups in peripheral blood [(1.81 ± 0.19)%, (3.74 ± 0.55)%] and BALF [(7.84 ± 0.28)%, (8.01 ± 0.39)%] compared with the12 wk [(0.97 ± 0.08)%, (5.64 ± 0.54)%] and the 24 wk control group [(1.08 ± 0.10)%, (5.95 ± 0.48)%]. Ratio of Treg in BALF was higher in the smoke-exposure groups [(8.81 ± 0.49)%, (11.98 ± 0.72)%] compared with the control groups [(4.34 ± 0.28)%, (5.21 ± 0.42)%]. The level of IL-17 mRNA was increased in the 12 wk and the 24 wk smoke-exposure group in peripheral blood (25.7 ± 2.0, 33.9 ± 1.5) and in BALF (22.2 ± 1.8, 34.7 ± 4.2) compared with the 12 wk (11.3 ± 2.6, 11.6 ± 2.4) and the 24 wk (11.1 ± 2.0, 13.5 ± 3.4) control groups. Foxp3 mRNA was increased in the smoke-exposure groups (24.4 ± 2.7, 30.3 ± 2.7) compared with the control groups (12.7 ± 2.7, 14.6 ± 3.8). Th17 in smoke-exposure groups was positively correlated with counts of total cells and macrophages (r = 0.512, 0.543, all P < 0.05). CONCLUSIONS: An elevated expression of Th17 and Treg cells and an increase of inflammatory cytokines were evident in airway inflammation of cigarette smoke-exposed rats, suggesting that Treg was involved in the immunological regulation and Th17 was associated with the persistent inflammation in cigarette smoke-induced airway inflammation in rats.

[Change of airway inflammation induced by Th1/Tc1 and the expression of T regulatory cells in smoking cessation rats].

OBJECTIVE: to study the change of airway inflammation induced by Th1/Tc1 and the expression of CD4(+)CD25(+) regulatory T cells (Treg) in smoking cessation rats. METHODS: fifty healthy male Wistar rats were randomly divided into five groups: 12-week normal control (group A, n = 10), 24-week normal control (group B, n = 10), 12-week smoke exposure (group C, n = 10), 24-week smoke exposure (group D, n = 10) and smoking cessation (group E, n = 10). Groups C, D and E were exposed to cigarettes for 12 weeks. At Week 12, groups A and C were sacrificed. Group D continued smoke exposure and group E had smoking cessation for 12 weeks. At Week 24, groups B, D and E were sacrificed. Pathomorphological changes of small airway were analyzed. The cells in BALF (bronchoalveolar lavage fluid) were collected and analyzed by absolute and differential cell counts. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of IFN-γ, IL-4, IL-8 and TNF-α. And flow cytometry was employed to determine the Foxp3 + Treg cell populations and reverse transcription-polymerase chain reaction (RT-PCR) to assay the mRNA expression for Foxp3. RESULTS: (1) compared with groups A and B, the airway inflammation score of groups C, D and E increased significantly (all P < 0.01). Compared with group C, the airway inflammation score of groups D and E both increased (all P < 0.01), especially group D; (2) compared with groups A and B, the levels of IFN-γ, TNF-α and IL-8 in groups C, D and E increased (all P < 0.01) while those of IL-4 decreased. The levels of IFN-γ, TNF-α and IL-8 showed no difference between groups C and E. The levels of IFN-γ, TNF-α and IL-8 were higher in group D than those in groups C and E; (3) the ratio of Foxp3 + Treg cells in BALF was higher in group C (7.4% ± 0.8%), group D (7.8% ± 1.7%) and group E (7.0% ± 1.4%) than group A (4.8% ± 1.2%) and group B (4.7% ± 1.2%) (all P < 0.01). There were no differences in the ratio of Foxp3 + Treg cells among groups C, D and E (all P < 0.05); (4) there was an elevated expression of Foxp3 mRNA in group C (0.22 ± 0.02), group D (0.23 ± 0.03), group E (0.20 ± 0.04) versus group A (0.13 ± 0.01) and group B (0.11 ± 0.02) (all P < 0.01). But there was no difference in the expression of Foxp3 mRNA among groups C, D and E (all P > 0.05). CONCLUSIONS: airway inflammation induced by Th1/Tc1 and an elevated expression of Treg cells in BALF are found in smoke exposure rats. Upon smoking cessation, the above-mentioned airway inflammation still persists and the expression of Treg cells in BALF shows no decrease. It suggests that an immune imbalance may be involved in the progression of Th1/Tc1-induced airway inflammation upon smoking cessation.

[CD4(+)Foxp3(+) regulatory T cells in inflammation and emphysema after smoking cessation in rats].

OBJECTIVE: To evaluate the expression of Treg in a cigarette smoke-induced rat model of emphysema and after smoking cessation in the rats. METHODS: Fifty male Wistar rats were randomly divided into control group 1 (12 weeks), control group 2 (24 weeks), smoke-exposure group 1 (12 weeks), smoke-exposure group 2 (24 weeks) and smoking cessation group, with 10 rats in each group. Alveolar airspace enlargement was observed by hematoxylin-eosin (HE) staining. IL-8 and TNF-α levels in bronchoalveolar lavage fluid (BALF) were tested by ELISA. The proportion of CD4(+)Foxp3(+) Treg in peripheral blood and lungs of rats was determined by flow cytometry. The mRNA expression of Foxp3 was measured by real-time PCR. Comparisons of the data between different groups were performed using one-way ANOVA, and SNK and Games-Howell test was used for comparison between 2 groups. RESULTS: The mean linear intercept (MLI) in smoke-exposure group 1 and group 2 [(64.9 ± 5.3) µm, (77.9 ± 11.5) µm] was higher than those in the control group 1 and group 2 [(39.0 ± 3.8) µm, (40.3 ± 2.7) µm], all P < 0.01. Compared with smoke-exposure group 2, the MLI in smoking cessation group (71.5 ± 5.8) µm showed a lower value (P < 0.01), but still higher than that in smoke-exposure group 1 (P < 0.01). The IL-8 and TNF-α levels in BALF of smoke-exposure group 1 and group 2 [(68 ± 17) ng/L, (85 ± 16) ng/L], [(14.1 ± 1.8) ng/L, (20.1 ± 8.7) ng/L] were higher than those in control group 1 and group 2 [(44 ± 8) ng/L, (43 ± 9) ng/L], [(6.3 ± 2.3) ng/L, (5.8 ± 1.6) ng/L], all P < 0.05. The IL-8 and TNF-α levels were not statistically different between in smoking cessation group (56 ± 6) ng/L, (14.7 ± 4.7) ng/L and smoke-exposure group 1. The percentage of Treg in the lungs of smoke-exposure group 1 and group 2 [(6.6 ± 0.8)%, (5.3 ± 0.9)%] was significantly decreased as compared to control group 1 and group 2 [(9.0 ± 1.0)%, (9.6 ± 0.9)%], all P < 0.01. The percentage of Treg in lungs was not statistically different between smoke-exposure group 1 and smoking cessation group (7.2 ± 0.6)%. In peripheral blood, there was no significant difference between groups in the percentage of Treg. In the lung, Foxp3 mRNA expression in smoke-exposure group 1 and group 2 [(17 ± 7), (9 ± 7)] was less than that in control group 1 and group 2 [(39 ± 6), (42 ± 7)], all P < 0.01. The Foxp3 mRNA expression was not statistically different between smoke-exposure group 1 and smoking cessation group (21 ± 9). No significant differences in peripheral blood Foxp3 mRNA expression was found between groups. CONCLUSIONS: Decreased Treg was present in lungs of cigarette smoke-induced model of emphysema despite 12 weeks' smoking cessation, suggesting that down-regulation of Treg may be involved in the amplified and persistent inflammation after smoking cessation.

Association between the IL1B, IL1RN polymorphisms and COPD risk: a meta-analysis.

The interleukin-1 (IL-1) gene polymorphisms have been implicated in chronic obstructive pulmonary disease (COPD) risk, but results are controversial. We aimed to conduct a meta-analysis to address this issue. Odds ratio (OR) and 95% confidence interval (CI) were used to investigate the strength of the association. The meta-analysis revealed no association between the IL1B (-511), (-31), (+3954) polymorphisms and COPD risk. However, stratification by ethnicity indicated that the T allele carriers of the IL1B (-511) polymorphism and the C allele carriers of the IL1B (-31) variant were associated with an increased risk for developing COPD in East Asians (OR = 1.61, 95% CI: 1.13-2.31, Pz = 0.009 and OR = 1.55, 95% CI: 1.14-2.11, Pz = 0.006, respectively). The meta-analysis revealed a significant association between the IL1RN (VNTR) polymorphism and COPD risk in all study subjects and East Asians under homozygote model (22 vs. LL: OR = 3.16, 95% CI: 1.23-8.13, Pz = 0.017 and OR = 3.20, 95% CI: 1.13-9.12, Pz = 0.029, respectively). Our meta-analysis suggests that the IL1B (-511), (-31) and IL1RN (VNTR) polymorphisms are associated with COPD risk in East Asians. There is no association between the IL1B (+3954) polymorphism and COPD risk. Further studies should be performed in other ethnic groups besides East Asians.

Association between tumor necrosis factor-α-308G/A polymorphism and obstructive sleep apnea: a meta-analysis.

BACKGROUND AND OBJECTIVE: The tumor necrosis factor (TNF)-α-308G/A polymorphism has been implicated in susceptibility to obstructive sleep apnea (OSA). However, results from previous studies are inconsistent. A systematic review and meta-analysis of the published studies was performed to investigate this association. METHOD: We searched PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Weipu databases for published studies evaluating the association between -308G/A polymorphism and OSA. Data were extracted using standardized forms and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. RESULTS: Four case-control studies involving a total of 419 cases and 460 controls were included in the meta-analysis. Combined data indicated that individuals carrying the -308A allele had a 65% increased risk of developing OSA when compared with the GG homozygotes (OR=1.65, 95% CI=1.02-2.68, p=0.04). In adults, the risk was even higher, elevated by 100% (OR=2.00, 95% CI=1.26-3.18, p=0.003). CONCLUSION: The TNF-α-308G/A polymorphism contributes to the risk of OSA, especially in adults.