A Disintegrin And Metalloproteinase 33 Research Articles

ADAM33 Silencing Inhibits Vascular Smooth Muscle Cell Migration and Regulates Cytokine Secretion in Airway Vascular Remodeling via the PI3K/AKT/mTOR Pathway.

Introduction Vascular smooth muscle cells (VSMCs) are highly involved in airway vascular remodeling in asthma. Objectives This study aimed to investigate the mechanisms underlying the effects of a disintegrin and metalloproteinase-33 (ADAM33) gene on the migration capacity and inflammatory cytokine secretion of VSMCs. Methods Human aortic smooth muscle cells (HASMCs) were transfected with lentiviral vectors carrying short hairpin RNA (shRNA) targeting ADAM33 or negative control vectors. The migration capacity of HASMCs was evaluated by a transwell assay. The levels of secreted inflammatory cytokines were measured using enzyme-linked immunosorbent assay (ELISA) kits. Reverse transcription-quantitative polymerase chain reaction and Western blot assays were performed to detect mRNA and protein expression levels. Results Silencing of ADAM33 significantly inhibited the migration of HASMCs. The expression of tumor necrosis factor alpha (TNF-α) in the supernatant of HASMCs was decreased, while that of interferon gamma (IFN-γ) was increased after the transfection of shRNA targeting ADAM33. Insufficient ADAM33 expression also suppressed the expression levels of phosphatidylinositol 3-kinase (PI3K), phospho-protein kinase B (AKT), phospho-mammalian target of rapamycin (mTOR), Rho-associated protein kinases, phospho-forkhead box protein O1 (FOXO1), and cyclin D1, but it did not affect the levels of AKT, mTOR, or Rho. Conclusion Silencing of the ADAM33 gene inhibited HASMC migration and regulated inflammatory cytokine secretion via targeting the PI3K/AKT/mTOR pathway and its downstream signaling. These data contribute to a better understanding of the regulatory mechanisms of airway vascular remodeling in asthma.

Silencing a disintegrin and metalloproteinase‑33 attenuates the proliferation of vascular smooth muscle cells via PI3K/AKT pathway: Implications in the pathogenesis of airway vascular remodeling.

Accumulating evidence suggests that pulmonary expression of a disintegrin and metalloproteinase-33 (ADAM33) serves a key role in the pathogenesis of airway remodeling-related diseases, including asthma. Airway vascular proliferation has been recognized as a key feature of airway remodeling. Our previous study showed that ADAM33 is constitutively expressed in airway vascular smooth muscle cells in patients with asthma, suggesting a potential role of ADAM33 in regulating airway vascular remodeling. Using in vitro human aortic smooth muscle cells (HASMCs) and lentiviral vector carrying short hairpin RNA for ADAM33, the present study aimed to evaluate the influence of ADAM33 silencing on the proliferation and apoptosis of HASMCs and the underlying molecular pathways. Cellular proliferation was observed using the Cell Counting Kit-8 method. Cellular apoptosis was evaluated with Annexin V-PE/7-AAD staining and flow cytometry. Reverse transcription-quantitative PCR and western blotting were used to evaluate the changes in mRNA and protein levels of involved signaling molecules. It was found that silencing of ADAM33 expression in HASMCs significantly inhibited proliferation, but induced the apoptosis of HASMCs. These changes were accompanied by inhibition of the PI3K/AKT/ERK pathway and Bcl-2, but an increase in Bax expression. These results suggested that constitutive expression of ADAM33 may be important to maintain a proliferative phenotype in HASMCs. The influences of ADAM33 on proliferation and apoptosis of HASMCs may involve regulation of PI3K/AKT/ERK and Bax/Bcl-2 pathways. These findings suggested an important role of ADAM33 in airway vascular remodeling and potential therapeutic significance of ADAM33 inhibition in airway remodeling-related diseases.

Association of ADAM33 T1 Polymorphism With Subgroups of Pediatric Asthma Patients in Iran

There is strong evidence on the interaction of several genetic variations and environmental conditions in the etiology of asthma. Association of a disintegrin and metalloproteinase 33 (ADAM33) with asthma risk is not clear and shows diversity between nations and ethnicities. Several single nucleotide polymorphisms (SNP) of the ADAM33 gene are introduced and studied according to the disease onset and characteristics. The aim of our study is to determine the association of ADAM33 rs2280091 polymorphism and pediatric asthma in the Iranian population. A total of 63 asthma patients (aged 6-18) and 86 healthy controls were enrolled in our study. Asthma type, classification, and severity were defined. SNPs of the ADAM33 gene at rs2280091 (T1) were analyzed. Pulmonary function tests, total blood eosinophil count, and IgE count were also assessed. T1 genotype and allele frequencies were not associated with asthma risk in Iranian pediatric asthma. Atopic asthma subgroup and patients with normal eosinophil count showed association with ADAM33 rs2280091. Moreover, asthma patients with AG genotype showed lower pulmonary functions.

ADAM 33 gene V4 C/G rs2787094 polymorphism in psoriasis.

Psoriasis is a common chronic inflammatory disease. A disintegrin and metalloproteinase 33 (ADAM33) gene is the first novel susceptibility gene for asthma. The aim of this study was to investigate the relationship of ADAM 33 gene V4 C/G rs2787094 polymorphism with the risk of psoriasis in the Turkish population. ADAM33 gene polymorphism (V4 C/G rs2787094) was analyzed in 97 psoriasis patients and 50 healthy control subjects. This study was performed by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analysis. There was no significant difference in ADAM33 genotype and allele distributions between psoriasis and control groups (p > 0.05). ADAM33 V4 C/G rs2787094 polymorphism was not associated with psoriasis risk in the Turkish population. Larger studies with different ethnicities are needed to determine the impact of ADAM33 polymorphism on the risk of developing psoriasis (Tab. 3, Fig. 1, Ref. 16).

T1 polymorphism in a disintegrin and metalloproteinase 33 (ADAM33) gene may contribute to the risk of childhood asthma in Asians.

Polymorphisms in ADAM33 gene have been implicated in susceptibility to the risk of childhood asthma. However, the results remain controversial. We performed meta-analyses to clarify the relationship between them. Relevant articles were searched in PubMed, Embase, Wanfang, and China National Knowledge Infrastructure. The Odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of the associations. Fourteen studies with five ADAM33 polymorphisms (F + 1, T1, T2, S2, and V4) were identified, involving 2687 cases and 2996 controls. ADAM33 F + 1, T2, and T1 polymorphisms showed significant associations with asthma risks in the overall and Caucasian children, Asian children, and Caucasian and Chinese children, respectively; however, these significant results were unstable in sensitivity analysis. T1 revealed significant and stable associations with asthma risks among Asian children in the dominant (OR = 2.00, 95% CI = 1.40-2.87, P = 0.0002) and codominant (OR = 3.06, 95% CI = 1.71-5.50, P = 0.0002) models; in cumulative meta-analyses, these significant results were robust. Concerning S2 or V4 polymorphism, no significant associations were observed. These findings demonstrate that ADAM33 T1 polymorphism might be a potential susceptible predictor of asthma for Asian children. Further functional studies between this polymorphism and asthma risks are warranted.

Overexpression of soluble ADAM33 promotes a hypercontractile phenotype of the airway smooth muscle cell in rat

A disintegrin and metalloproteinase 33 (ADAM33) has been identified as a susceptibility gene for asthma, but details of the causality are not fully understood. We hypothesize that soluble ADAM33 (sADAM33) overexpression can alter the mechanical behaviors of airway smooth muscle cells (ASMCs) via regulation of the cell's contractile phenotype, and thus contributes to airway hyperresponsiveness (AHR) in asthma. To test this hypothesis, we either overexpressed or knocked down the sADAM33 in rat ASMCs by transfecting the cells with sADAM33 coding sequence or a small interfering RNA (siRNA) that specifically targets the ADAM33 disintegrin domain, and subsequently assessed the cells for stiffness, contractility and traction force, together with the expression level of contractile and proliferative phenotype markers. We also investigated whether these changes were dependent on Rho/ROCK pathway by culturing the ASMCs either in the absence or presence of ROCK inhibitor (H1152). The results showed that the ASMCs with sADAM33 overexpression were stiffer and more contractile, generated greater traction force, exhibited increased expression levels of contractile phenotype markers and markedly enhanced Rho activation. Furthermore these changes were largely attenuated when the cells were cultured in the presence of H-1152. However, the knock-down of ADAM33 seemed insufficient to influence majority of the mechanical behaviors of the ASMCs. Taken together, we demonstrated that sADAM33 overexpression altered the mechanical behaviors of ASMCs in vitro, which was most likely by promoting a hypercontractile phenotype transition of ASMCs through Rho/ROCK pathway. This revelation may establish the previously missing link between ADAM33 expression and AHR, and also provide useful insight for targeting sADAM33 in asthma prevention and therapy.

Genetic variants of ADAM33 are associated with asthma susceptibility in the Punjabi population of Pakistan

Objective: A disintegrin and metalloproteinase 33 (ADAM33) gene has been considered as an asthma susceptibility gene due to its possible role in airway remodeling, abnormal cell proliferation, and differentiation. Association of this gene with asthma has been reported in several genetic studies on various populations. The current study aims to evaluate the association of ADAM33 gene polymorphisms with the risk of asthma in the Punjabi population of Pakistan. Method: A total of 101 asthma patients and 102 age-matched healthy controls from Lahore, a city in Punjab, were recruited. ADAM33 single nucleotide polymorphisms (SNPs) T + 1[rs2280089], T2[rs2280090], T1[rs2280091], ST + 5[rs597980], ST + 4[rs44707], S2[rs528557], Q − 1[rs612709], and F + 1[rs511898] were genotyped in both patients and controls using single base extension and capillary electrophoresis-based genetic analyzer. The basic allelic and genotypic model was analyzed for association of the SNPs with asthma using SHEsis software. Haploview software was used to calculate pairwise linkage disequilibrium (LD) among six of the genotyped SNPs. Results: Of the 8 SNPs genotyped, only S2[rs528557] showed significant association with asthma (Allele p = 0.0189, Genotype p = 0.021). SNPs T + 1[rs2280089], T2[rs2280090], T1[rs2280091], ST + 4[rs44707], S2[rs528557], and Q − 1[rs612709] were found to be in moderate to strong LD. The significantly higher frequency of haplotype “AAGTCG” in healthy controls suggests a protective effect against asthma risk in the studied population (p = 0.0059). Conclusion: These findings suggest that genetic variants of ADAM33 gene may play important roles in asthma susceptibility in the Punjabi population of Pakistan.

Association of ADAM33 gene S1 and S2 transmembrane domain polymorphisms in COPD from South-Indian population

BackgroundChronic obstructive pulmonary disease (COPD) is defined as a disease characterised by partially reversible and progressive airflow limitation associated with an abnormal inflammatory response of the lung with systemic manifestation. COPD is influenced by both environmental and genetic factors. ADAM33 (a disintegrin and metalloproteinase 33) has been one of the most exciting candidate genes for asthma and it was first associated with the disease in Caucasian populations. Recently, ADAM33 was shown to be associated with excessive decline of lung function and COPD. The aim of the study was to investigate the association of ADAM33 – S1 and S2 polymorphisms with COPD. Subjects and methodsA total of 150 COPD patients attending the Department of Pulmonary Medicine, Government Chest Hospital, Erragadda, Hyderabad, India and 200 healthy control subjects were considered for the present study. A standard PCR–RFLP method was carried out for genotyping of ADAM33 S1-A/G and S2-C/G polymorphisms in all the participants. ResultsGenotypic distribution of the control and patient groups was compared with values predicted by the Hardy–Weinberg equilibrium, odds ratios (OR) and their respective 95% confidence intervals were used to measure the strength of association between ADAM33 S1 (A/G) and S2 (C/G) gene polymorphisms and COPD. The genotypic frequencies of ADAM33 gene S1 (A/G) polymorphism were found to be AA/AG/GG – 36%, 56%, 8% in controls and 5.33%, 10.66%, 84% in COPD cases, respectively. Genotypic frequencies for S2 (C/G) polymorphism were found to be CC/CG/GG – 14.47%, 78.20%, 5.92% in controls and 4%, 8% and 88% in COPD cases, respectively. There is a significant difference in distribution of genotypes and alleles of ADAM33 S1 and S2 gene polymorphisms between the two groups. ConclusionThe present study suggests that the ADAM33 S1 and S2 gene promoter polymorphisms can be the major genetic predisposing factors in the aetiology of COPD.

ADAM33 polymorphisms and susceptibility to allergic rhinitis: a meta-analysis.

Several polymorphisms in a disintegrin and metalloproteinase 33 (ADAM33) have been implicated in susceptibility to allergic rhinitis (AR), but the results are inconclusive. This meta-analysis was aimed to clarify the impact of ADAM33 polymorphisms on AR risk. Pubmed, EMBASE and Cochrane library were searched until 11 October 2013 for eligible studies on seven ADAM33 polymorphisms: T1, T2, S1, S2, V4, Q-1 and T+1. Data were extracted, and pooled odd ratios (ORs) as well as 95 % confidence intervals (CIs) were calculated. Six studies with 1,135 AR patients and 1,565 controls were included. It was found that ADAM33 T1 (AG+GG vs. AA, OR 1.47, 95 % CI 1.23-1.75, I (2) = 94 %; G vs. A, OR 1.53, 95 % CI 1.32-1.78, I (2) = 94 %), T2 (GA+AA vs. GG, OR 1.26, 95 % CI 1.06-1.51, I (2) = 92 %; G vs. A, OR 1.27, 95 % CI 1.08-1.50, I (2) = 92 %), V4 (CG+GG vs. CC OR 1.35, 95 % CI 1.14-1.59, I (2) = 95 %;G vs. C OR 1.28, 95 % CI 1.13-1.44, I (2) = 96 %) and Q-1 (GA+AA vs. GG OR 1.55, 95 % CI 1.24-1.95, I (2) = 74 %; G vs. C OR 1.46, 95 % CI 1.19-1.79, I (2) = 73 %) polymorphisms were significantly associated with AR susceptibility but not S1, S2 and T+1. In Asians, the same result was found. This meta-analysis indicated that ADAM33 T1, T2, V4 and Q-1 polymorphisms may be the risk factors which conferred to AR susceptibility. The differences in ethnicity did not influence the associations obviously. Gene-gene and gene-environment interactions should be investigated in the future.

Association of ADAM33 gene polymorphisms with psoriasis in a northeastern Chinese population

Psoriasis (PS) is a common hyperproliferative and chronic inflammatory disease of the skin. It is influenced by both genetic and environmental factors. The ADAM33 (a disintegrin and metalloproteinase 33) gene located on chromosome 20p13, has recently been identified as an asthma-susceptibility gene by positional cloning. Recently, ADAM33 has been suspected to be associated with PS. To study the association between ADAM33 and PS in the northeastern Chinese population. A total of 240 PS patients and a control group of 237 healthy volunteers were recruited for this study. Five polymorphic loci (V4, T+1, T2, T1, S2) of ADAM33 were selected for genotyping. Genotypes were determined by using the polymerase chain reaction-restriction fragment length polymorphism method. We observed the frequency of the rs2787094 C allele was significantly higher in cases than in controls (50 vs. 33%, P < 0.0001).Similarly, the rs528557 C allele exhibited a significantly increased frequency in PS patients compared with healthy controls (35 vs. 21%, P < 0.0001). We also found that the frequencies of H3 (CGGAC), H6 (CGGGG) haplotypes were significantly higher in the case group than in the control group (P = 0.006, 0.028, respectively). In contrast, the haplotype H9 (GAAAG) was more common in the control group than in the case group (P = 0.018). Our data suggest that the ADAM33 polymorphisms may be associated with PS in the northeastern Chinese population.

ADAM metallopeptidase domain 33 (ADAM33): a promising target for asthma.

Over the last few years, a significant progress has been made in understanding the role of a disintegrin and metalloproteinase 33 (ADAM33) in asthma. The previous observations for the association with asthma have been replicated in over 33 different population samples worldwide. We and others have performed association analysis and meta-analysis and provided further evidence that several polymorphisms in the ADAM33 are risk factors for asthma, especially in the Asian population. Further, several studies have suggested that alterations in epigenetic marks alter the patterns of DNA methylation of ADAM33 and result in potentially adverse biological effects. Finally, while the biological activities of ADAM33 are as yet unknown, ADAM33 may play a possible role in airway remodeling because of its high expression in epithelium, myo/fibroblasts, and airway smooth muscle cells (ASMCs) and its role in promoting angiogenesis and stimulating cell proliferation and differentiation. Thus, ADAM33 represents a promising target for asthma. However, further investigations are clearly needed to discover functional ADAM33 gene polymorphisms and the role of genetic/epigenetic factors in conferring genetic susceptibility to environmental exposure induced asthma as well as biological function in asthma. This, in turn, will unlock the possibility of ADAM33 as a target for asthma therapy.

Association between polymorphisms in ADAM33, CD14, and TLR4 with asthma in the Uygur population in China.

We evaluated the associations between single nucleotide polymorphisms (SNPs) and haplotypes of the genes encoding a disintegrin and metalloproteinase 33 (ADAM33), cluster of differentiation 14 (CD14), and Toll-like receptor 4 (TLR4) and the susceptibility of developing specific adult phenotypes of bronchial asthma in a Chinese Uygur population. Five SNPs of ADAM33 (T1, T2, and V4), 3 SNPs of CD14 (-1359G/T, -1145G/A, and -159T/C), and 2 SNPs of TLR4 (-896A/G and -1196C/T) were genotyped in a Chinese Uygur sample of 126 adult asthmatic patients and 126 control subjects. Gene polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism analysis. The genotyping results were confirmed in a random subgroup of our samples using direct DNA sequencing. The allele frequencies of ADAM33 T1 (TC), T2 (AG), and V4 (GG) were significantly higher in patients than in controls (P<0.05). The genotypes T1 (TC+CC), T2 (AG+AA), and V4 (CG+GG) significantly increased the risk of asthma. After adjusting for confounding factors, these associations were stronger and remained significant. The T1 (TC) and V4 (GG) genotypes in the ADAM33 gene were associated with significantly decreased FEV1 levels in patients with asthma. The haplotype frequencies of Hap3 (CAC) and Hap4 (CAG) were significantly higher in patients than in controls (P<0.05). Our results suggest that polymorphisms T1, T2, and V4 in ADAM33 may contribute to the susceptibility to asthma. Specific haplotypes of ADAM33 may contribute to a higher susceptibility to asthma in the Chinese Uygur population.

Association of a disintegrin and metalloproteinase 33 (ADAM33) gene polymorphisms with chronic obstructive pulmonary disease in the Chinese population: a meta-analysis.

Numerous studies have evaluated the association between polymorphisms of a disintegrin and metalloproteinase 33 (ADAM33) gene and chronic obstructive pulmonary disease (COPD) risk; however, the results remain conflicting. The aim of this study was to investigate whether ADAM33S2 and -T1 polymorphisms are associated with susceptibility to COPD risk in the Chinese population. Publications addressing the association between ADAM33S2 or T1 polymorphisms and COPD risk were selected from the PubMed, Cochrane Library, Embase, CNKI, and Wanfang databases. Two independent reviewers extracted data from the studies. Statistical analysis was performed using the RevMan 5.0.25 and STATA 11.0 software. Six case-control studies were retrieved, including a total of 1201 COPD patients and 1203 controls. Meta-analysis results showed a significant association between the T1 polymorphism and COPD risk in both dominant model [odds ratio (OR) = 2.54, 95% confidence interval (CI) = 1.40-4.61, P = 0.002] and recessive model (OR = 3.50, 95%CI = 2.11-5.81, P < 0.00001) comparisons. For S2, no significant association was found in any genetic model. This suggests that the T1 polymorphism of ADAM33 would increase the risk of COPD in a Chinese individual, whereas the S2 polymorphism might not be a risk factor for COPD. To further evaluate the gene-to-gene and gene-to-environment interactions on ADAM33 genetic variations and COPD risk, more studies using large sample sizes of patients are needed.

ADAM33 protein expression and the mechanics of airway smooth muscle cells are highly correlated in ovalbumin-sensitized rats

A disintegrin and metalloproteinase 33 (ADAM33) has been identified as an asthma susceptibility gene; however, the role of ADAM33 in the pathogenesis and progression of asthma remains to be elucidated. As ADAM33 is predominantly expressed in airway smooth muscle cells (ASMCs), it is feasible to investigate whether ADAM33 protein expression is correlated with ASMC mechanics that are ultimately responsible for airway hyperresponsiveness in asthma. To determine this, Sprague Dawley rats were sensitized with ovalbumin (OVA) for up to 12 weeks to simulate asthma symptoms. Subsequently, ASMCs were isolated from the rats and cultured in vitro. The protein expression of ADAM33 and cytoskeletal proteins (including F‑actin and vinculin), cell stiffness and contractility, as well as traction force were measured. The results demonstrated that compared with the non‑sensitized rats, the protein expression of ADAM33 in ASMCs from the OVA‑sensitized rats increased in a time‑dependent manner, reaching a maximum level at 4 weeks of sensitization and gradually subsiding as OVA sensitization continued (P<0.001). The cell stiffness, traction force and expression of vinculin and F‑actin changed similarly, resulting in a positive correlation with ADAM33 protein expression (Pearson's correlation coefficient, 0.864, 0.716, 0.774 and 0.662, respectively; P=0.1‑0.3). The in vivo results of OVA‑induced ADAM33 protein expression and its association with the mechanics of ASMCs suggested that ADAM33 is a mediator of ASMC dysfunction in asthma, and may provide a rationale for the therapeutic targeting of ADAM33 in the treatment of asthma.

The Methylation Patterns of a Disintegrin and Metalloproteinase 33 Gene (ADAM33) in Adult Asthma

Background: Asthma is a common chronic inflammatory respiratory disease. Previous studies have suggested that the pathogenesis of asthma may be affected by epigenetic regulation. The purpose of this study is to characterize the effect of the methylation of each CpG site in the ADAM33 (a disintegrin and metalloproteinase 33) gene in adult asthma. Methods: A human CpG island microarray was used to examine 4 asthmatic cases and 4 healthy controls, and the results suggested that there might be differences in methylation within exon 9 of the ADAM33 gene. Therefore, we designed a case-control study with 50 asthmatic patients and 50 age- and sex-matched healthy controls to examine the relationship between the CpG methylation of the ADAM33 gene and asthma using bisulfite deoxyribonucleic acid modification and sequencing. Results: Bisulfite sequencing experiments showed that the 14 CpG sites in exon 9 of the ADAM33 gene were highly methylated (100%) in all individuals. The proportions of methylation of the 14 CpG sites in ADAM33 in the case group were not different from those of the control group. The methylation of exon 9 of this locus was not associated with age, sex, IgE levels, or lung function. This study found no association between the methylation of CpG sites in exon 9 of the ADAM33 gene and adult asthma. Conclusions: The 14 CpG sites were highly methylated in the case and control groups. Further investigation of exon 9 in ADAM33 in a larger population is needed to evaluate its role in asthma.

A disintegrin and metalloproteinase 33 (ADAM33) gene polymorphism association with asthma in Egyptian children

A disintegrin and metalloproteinase-encoding gene (ADAM33), was recently identified as an asthma susceptibility gene. ADAM33 protein is expressed in smooth muscle cells of bronchi and pulmonary fibroblasts, playing a major role in airway remodeling. Earlier studies, have mostly confirmed a link between ADAM33 and asthma as well as bronchial hyperresponsiveness. This work studied a group of Egyptian asthmatic children for 3 ADAM33 single nucleotide polymorphisms (SNPs), previously identified as putative risk alleles: T1 G>A(rs2280091), T2 A>G(rs2280090), V4 G>C(rs2787094) using Polymerase Chain Reaction – restriction fragment length polymorphism (PCRRFLP) with emphasis on their relation to clinical (severity, smoking, family history, and atopic manifestations) and laboratory data (Ig Immunoglobulin E (Ig E) level and absolute eosinophilia) and pulmonary functions. Sixty (3–12years old) asthmatic children and 32 matched controls were recruited. The genotype distribution for the SNPs showed no significant difference between the patients and the controls. A higher frequency of the (AA) genotype of T1 polymorphism was found in controls (75%) than in patients (41%), while the (AG) variant was higher in cases (46.6%) than in controls (21.9%) but with no statistically significant difference. Also the (GG) genotype was higher in cases (11.6%) than in controls (3.1%) but with no statistical significance. The allelic frequencies of T1 showed a higher (A) allele in controls (85.93%) than cases (65%) and higher (G) allele in cases (35%) than controls (14.06%), showing a high significant difference. No correlation was found between (T1, T2, and V4) and the demographic, clinical and laboratory parameters, except SNP T1 showing a positive correlation with Ig E level, and SNP V4 showing a positive correlation with passive smoking as a precipitating factor and borderline significance with absolute eosinophilia. In conclusion, no significant association was detected between these SNPs and asthma susceptibility in this study.

Association of ADAM33 gene polymorphisms with asthma in a Chinese population

Asthma is a very common disease involving genetic and environmental factors. A disintegrin and metalloproteinase 33 (ADAM33) has been one of the most exciting candidate genes for asthma since its first association with the disease in the white population. Recently, studies on the association of ADAM33 gene polymorphisms with the risk of asthma have been controversial. We therefore focused on testing the hypothesis that either single-nucleotide polymorphisms (SNPs) of the ADAM33 gene may be associated with asthma risk. The aim of this study was to evaluate the potential relationship between polymorphisms of ADAM33 and asthma in a Han population in China. A case control study was conducted in a Han population of eastern Chinese population. A total of 329 asthma patients and a control group of 316 healthy volunteers were recruited for this study. Four polymorphic sites (F+1, S2, T2 and V4) were selected for genotyping. Genotypes were determined by the allele-specific polymerase chain reaction with fluorescence melting curves and DNA sequencing method. Data were analysed using the chi-squared test software. Statistically significant differences in the distributions of the S2 site between patients and controls were observed (χ2=7.140, P<0.05). These preliminary results suggest an association between ADAM33 polymorphisms S2 C/G and asthma in a Chinese Han population. The SNPs (F+1 C/T, T2 G/A and V4 C/G) of the ADAM33 gene may be the causal variants in asthma disease, but the strength of this evidence is limited by our small sample size.

Association of ADAM33 Polymorphisms and Susceptibility to Psoriasis

Psoriasis (PS) is a common hyperproliferative and chronic inflammatory disease of the skin, which involves both genetic and environmental factors. The A disintegrin and metalloproteinase 33 (ADAM33) gene, located on chromosome 20p13, has recently been identified as an asthma-susceptibility gene by positional cloning. Recently, it has been reported that ADAM33 contributed to PS risk in the French population and white North Americans. To observe the relationship between ADAM33 gene and PS, a case-control study was conducted in a Han Chinese population. Three polymorphic sites (T1, T2, and V4) were genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis in 106 patients with PS and 125 healthy controls. We observed a decreased frequency in the CG genotype and GG genotype of ADAM33 rs2787094 (V4) in cases compared with controls (p = 0.045, odds ratio = 0.461, 95% confidence interval = 0.215-0.992, and p = 0.044, odds ratio = 0.447, 95% confidence interval = 0.203-0.987, respectively). Our data suggest that the ADAM33 gene may be associated with PS risk in the Chinese population.

Association of ADAM33 gene polymorphisms with COPD in a northeastern Chinese population

BackgroundChronic obstructive pulmonary disease (COPD) is influenced by both environmental and genetic factors. ADAM33 (a disintegrin and metalloproteinase 33) has been one of the most exciting candidate genes for asthma since its first association with the disease in Caucasian populations. Recently, ADAM33 was shown to be associated with excessive decline of lung function and COPD. The aim of this study was to evaluate the potential relationship between polymorphisms of ADAM33 and COPD in a Han population in northeastern China.MethodsA total of 312 COPD patients and a control group of 319 healthy volunteers were recruited for this study. Eight polymorphic loci (V4, T+1, T2, T1, S2, S1, Q-1, and F+1) of ADAM33 were selected for genotyping. Genotypes were determined by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.ResultsStatistically significant differences in the distributions of the T2G, T1G, S2C, and Q-1G alleles between patients and controls were observed (P < 0.001, odds ratio (OR) = 2.81, 95% confidence interval (CI) = 2.19-3.61; P < 0.001, OR = 2.60, 95% CI = 2.06-3.30; P = 0.03, OR = 1.31, 95% CI = 1.02-1.69; and P < 0.001, OR = 1.93, 95% CI = 1.50-2.50, respectively). Haplotype analysis showed that the frequencies of the CGGGGAGC, CGGGGAGT, CGGGCAGC, and CGGGGGGC haplotypes were significantly higher in the case group than in the control group (P = 0.0002, 0.0001, 0.0005, and 0.0074, respectively). In contrast, the haplotype CGAAGAGC was more common in the control group than in the case group (P < 0.0001).ConclusionThese preliminary results suggest an association between ADAM33 polymorphisms and COPD in a Chinese Han population.

Association of ADAM33 gene polymorphisms with adult allergic asthma and rhinitis in a Chinese Han population

BackgroundRhinitis and asthma are very common diseases involving genetic and environmental factors. Most patients with asthma also have rhinitis, which suggests the concept of 'one airway, one disease.' A disintegrin and metalloproteinase 33 (ADAM33) is the first asthma-susceptible gene to be discovered by positional cloning. To evaluate the potential influence of ADAM33 gene polymorphisms on allergic rhinitis (AR) and allergic asthma (AS), a case-control study was conducted on the Han population of northeast China.MethodsSix polymorphic sites (V4, T+1, T2, T1, S1, and Q-1) were genotyped in 128 patients with AR, 181 patients with AS, and 151 healthy controls (CTR). Genotypes were determined by the polymerase chain restriction fragment length polymorphism (PCR-RFLP) method. Data were analyzed using the chi-square test with Haploview software.ResultsThe single nucleotide polymorphisms (SNPs), V4 G/C, T+1 A/G, and T1 G/A, of the ADAM33 gene may be the causal variants in AR, whereas ADAM33 V4 G/C, T2 A/G, T1 G/A, and Q-1A/G may participate in the susceptibility of AS.ConclusionThese results suggest that polymorphisms of the ADAM33 gene may modify individual susceptibility to AR and AS in a Chinese Han population.