Search

Background and Objective Methods Results Conclusion A disintegrin and metalloprotease 33 (ADAM33) is associated with asthma susceptibility, and its genetic variations impact susceptibility and disease severity. However, the mechanisms remain unclear. This study aimed to investigate ADAM33 single nucleotide polymorphisms (SNPs) in childhood asthma susceptibility and explore their regulatory mechanisms.Eleven selected SNPs in ADAM33 were genotyped and identified the association with asthma susceptibility. In the validation cohort, we measured plasma sADAM33 levels and compared them with disease severity among children with different SNP genotypes. Computational predictions identified miRNAs targeting the SNP, and the impact of the SNP on miRNA regulation was confirmed using a dual luciferase reporter system. Finally, we validated the regulatory role of miRNAs on ADAM33 expression using an in vitro model with upregulated ADAM33 expression.Only rs3918400 was associated with asthma susceptibility. In the validation cohort, children with allergic asthma exhibited higher plasma sADAM33 levels. Among asthmatic children, those with the rs3918400 CT/TT genotype had higher sADAM33 levels, poorer asthma control, more severe airway hyper‐responsiveness, lower FEV1% and higher dust mite‐specific IgE activity compared to those with the CC genotype. miR‐3928‐5p bound strongly to the rs3918400 C allele and effectively reduced ADAM33 protein expression in CC genotype cells. However, the binding affinity of miR‐3928‐5p to the T allele was weaker, resulting in diminished negative regulation of protein expression.The rs3918400 SNP affects the negative regulation of ADAM33 by miR‐3928‐5p, potentially participating in a complex interplay of processes related to childhood asthma susceptibility. [ABSTRACT FROM AUTHOR]

Abstract Background Worldwide, Chronic Obstructive pulmonary disease (COPD) is a main cause of morbidity and mortality. Considering the global increase in the prevalence of COPD, research on the genetic factors that predispose to COPD is reviving. Recently, ADAM 33 has been found to be related to severe lung function decline and COPD. Aim and objective The present study is carried out with the main aim of determining the association of SNP, i.e., S2 (rs528557), with COPD. Method A case–control methodology is used to recruit participants. 50 COPD patients over 40 years of age and with a history of more than 20 pack years of cigarette smoking were enlisted. The same number of age and gender-matched controls with no COPD history were involved. PCR sequencing was used to analyze the genetic polymorphism of the ADAM 33 gene (SNP, i.e., S2 (rs528557). Statistical analysis was carried out using SPSS version 21. The Chi-square test was used to determine the difference in SNP rs528557 genotypes and alleles between controls and COPD. Results The findings of this study revealed that the G allele was present in all COPD cases (100%) and 72% of control (p =

Asthma is a complex chronic respiratory disease characterized by airway hyperresponsiveness, inflammation, and obstruction. Many genes have been identified as associated with asthma but none with such substantial significance as the ADAM33 gene due to its role in airway remodeling and bronchial hyperresponsiveness. This review summarizes the current knowledge on the genetic and functional aspects of ADAM33 in asthma pathogenesis. We highlight its genetic variants associated with asthma susceptibility and severity, as well as the functional effects of ADAM33 on airway remodeling, smooth muscle cell proliferation, and its interplay with environmental factors. Additionally, we discuss the potential clinical implications of ADAM33 as a therapeutic target for asthma management. [ABSTRACT FROM AUTHOR]

Thyroid cancer is the most prevalent endocrine malignancy globally; however, its underlying pathogenesis remains unclarified. Reportedly, alternative splicing is involved in processes such as embryonic stem and precursor cell differentiation, cell lineage reprogramming, and epithelial-mesenchymal transitions. ADAM33-n, an alternative splicing isoform of ADAM33, encodes a small protein containing 138 amino acids of the N-terminal of full-length ADAM33, which constructs a chaperone-like domain that was previously reported to bind and block the proteolysis activity of ADAM33. In this study, we reported for the first time that ADAM33-n was downregulated in thyroid cancer. The results of cell counting kit-8 and colony formation assays showed that ectopic ADAM33-n in papillary thyroid cancer cell lines restricted cell proliferation and colony formation. Moreover, we demonstrated that ectopic ADAM33-n reversed the oncogenic function of full-length ADAM33 in cell growth and colony formation in the MDA-T32 and BCPAP cells. These findings indicate the tumor suppressor ability of ADAM33-n. Altogether, our study findings present a potential explanatory model of how the downregulation of the oncogenic gene ADAM33 promotes the pathogenesis of thyroid cancer. [ABSTRACT FROM AUTHOR]

Tobacco smoking is the leading risk factor for many respiratory diseases. Several genes are associated with nicotine addiction, such as CHRNA5 and ADAM33. This research aims to evaluate the association of the polymorphisms rs16969968 (CHRNA5) and rs3918396 (ADAM33) in patients who developed severe COVID-19. We included 917 COVID-19 patients hospitalized with critical disease and oxygenation impairment. They were divided into two groups, tobacco-smoking (n = 257) and non-smoker (n = 660) patients. The genotype and allele frequencies of two single nucleotide variants, the rs16969968 (CHRNA5) and rs3918396 (ADAM33), were evaluated. The rs3918396 in ADAM33 does not show a significative association. We analyzed the study population according to the rs16969968 genotype (GA + AA, n = 180, and GG, n = 737). The erythrocyte sedimentation rate (ESR) shows statistical differences; the GA + AA group had higher values than the GG group (p = 0.038, 32 vs. 26 mm/h, respectively). The smoking patients and GA or AA genotype carriers had a high positive correlation (p < 0.001, rho = 0.753) between fibrinogen and C-reactive protein. COVID-19 patients and smokers carriers of one or two copies of the risk allele (rs16969968/A) have high ESR and a positive correlation between fibrinogen and C-reactive protein. [ABSTRACT FROM AUTHOR]

Asthma, an inflammatory disease of the lower and upper airways, is one of the most common diseases in society. Depending on the source and the population studied, the percentage of asthma patients ranges from 5% to as high as 15%. The development of asthma is believed to be caused by an overlap between the body's personal propensity to develop the disease and environmental factors. For years, scientists have been studying the genetic basis of asthma. For several years they have had a new weapon in their arsenal - the GWAS method. The use of this method has enabled researchers to discover the relationship between gene variants found in patients and an increased risk of developing asthma.

ADAM33 has been linked to airway structural changes in patients with asthma, leading to airway hyperresponsiveness, narrowing, and ultimately poor treatment responsiveness. This study aimed to evaluate the genetic association of ADAM33 SNPs with asthma, disease severity, and treatment responsiveness to ICS+LABA in the South Indian population. In this case–control study (486 controls and 503 cases), we performed genotyping using MassArray for six SNPs of ADAM33, namely rs2280091, rs2787094, rs3918396, rs67044, rs2853209, and rs3918392. We studied the association with asthma and treatment responsiveness to ICS+LABA, using genotype, allele frequency distribution, and haplotype analysis. A significant clinical finding of the study was that certain patients in the disease severity group (moderate and mild) showed poor or no improvement after a three-month follow-up of regular ICS+LABA therapy. Of the studied ADAM33 SNPs, rs2853209 showed an association with asthma. The further analysis of asthma patients according to disease severity suggested an association between moderate disease and the minor allele "T" for rs2853209. The homozygous minor allele of SNP rs2787094 was found to be associated with poorer lung function and the least lung-function improvement after three months of ICS+LABA therapy. The haplotype analysis of six SNPs showed a significant association between the rs2853209 and rs3918396 blocks and asthma. ADAM33 gene polymorphism has clinical relevance in terms of disease association and response to treatment. SNP rs2853209 seemed most relevant to asthma, and SNP rs2787094 could be a genetic marker for predicting response to ICS+LABA therapy in the study population. [ABSTRACT FROM AUTHOR]

Abstract Background Recent research has pointed out the important roles of epigenetic modifications in the development and persistence of allergic rhinitis (AR), especially in relation to DNA methylation of disease-associated genes. We investigated whether AR susceptibility genes were epigenetically regulated, and whether methylation modulation of these genes in response to early-life environment could be a molecular mechanism underlying the risk for AR onset in a cohort of children aged 3–6 years in China. Methods Peripheral blood mononuclear cell (PBMC) samples were collected from 130 children patients, aged 3–6 years and diagnosed with AR; and 154 matched controls to detect promoter methylation in 25 AR susceptibility genes with the MethylTarget approach. Methylation levels were compared for each CpG site, each amplified region, and each gene. In addition, the relationship among DNA methylation, early-life environmental risk factors and AR onset were assessed. Results Maternal allergic history (P = 0.0390) and pet exposure (P = 0.0339) were significantly associated with increased AR risk. Differential methylation analyses were successfully performed for 507 CpG sites, 34 amplified regions and 17 genes and significant hypomethylation was observed in the promoter region of ADAM33 in AR patients [multiple test-corrected (FDR) P-value

Background: Recent research has pointed out the important roles of epigenetic modifications in the development and persistence of allergic rhinitis (AR), especially in relation to DNA methylation of disease-associated genes. We investigated whether AR susceptibility genes were epigenetically regulated, and whether methylation modulation of these genes in response to early-life environment could be a molecular mechanism underlying the risk for AR onset in a cohort of children aged 3–6 years in China. Methods: Peripheral blood mononuclear cell (PBMC) samples were collected from 130 children patients, aged 3–6 years and diagnosed with AR; and 154 matched controls to detect promoter methylation in 25 AR susceptibility genes with the MethylTarget approach. Methylation levels were compared for each CpG site, each amplified region, and each gene. In addition, the relationship among DNA methylation, early-life environmental risk factors and AR onset were assessed. Results: Maternal allergic history (P = 0.0390) and pet exposure (P = 0.0339) were significantly associated with increased AR risk. Differential methylation analyses were successfully performed for 507 CpG sites, 34 amplified regions and 17 genes and significant hypomethylation was observed in the promoter region of ADAM33 in AR patients [multiple test-corrected (FDR) P-value < 0.05]. Spearman correlation analysis revealed that the hypomethylation of ADAM33 was significantly associated with higher eosinophil counts (Spearman's ρ: − 0.187, P-value = 0.037). According to the results of the multiple regression analysis, after adjusting for cofounders, the interaction of early-life pet exposure with methylation level of ADAM33 increased the risk for AR onset 1.423 times more in children (95% CI = 0.0290–4.109, P-value = 0.005). Conclusion: This study provides evidence that early-life pet exposure and low methylation level of ADAM33 increase AR risk in children, and the interaction between pet exposure and methylation level of ADAM33 may play an important role in the development of AR. [ABSTRACT FROM AUTHOR]

Abstract Background Asthma is a common complex chronic, inflammatory polygenic disease with heterogeneous manifestations, affecting individuals of all age groups and posing an immense burden on healthcare resources. A number of studies have identified the association between a disintegrin and metalloprotease 33 (ADAM33) polymorphisms and asthma risk, however, the results still remain inconclusive. The objective of the present study was to identify the effect of ADAM33 variants in asthma susceptibility. Methods Eligible case-control studies published between January 2000 and June 2018 was searched and retrieved from online electronic databases. The odds ratio (OR) with its 95% confidence interval (CI) was employed to calculate the effect. Results A total of 63 case-control studies were finally screened out, including 13,280 asthma patients and 13,340 controls. Eleven SNPs of ADAM33 gene were identified. Our results detected a significant association between ADAM33 T2, Q1, F + 1 and AA genotype of T + 1 polymorphisms and asthma risk in total population. Subgroup analysis by ethnicities showed that the alleles and genotypes of T2, Q1 and F + 1 polymorphisms were associated with asthma susceptibility among Asian populations, while V4 polymorphism was associated with asthma among Caucasian populations. Subgroup analysis by ages showed that T2, F + 1 and ST + 4 polymorphisms were associated with childhood asthma, while Q1 and V4 polymorphisms were associated with asthma risk in adults. Subgroup analysis by asthma severity showed that only the G allele of ADAM33 T1 polymorphism was associated with the severity of asthma when compared with the controls. In addition, T2, Q1 and F + 1 polymorphisms of ADAM33 were significantly associated with increased the asthma risk in Chinese asthma patients. Conclusions Our results found that T2, Q1 and F + 1 polymorphisms of ADAM33 gene might contribute to asthma risk. Future well-designed case-control studies with large population and more ethnicities are still needed to estimate the association.

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.

Objective(s): Asthma, the most frequent chronic respiratory disease, results from a complex interaction between multiple genes and environmental factors. To date, more than 100 candidate genes and single nucleotide polymorphisms (SNPs) have been reported to be associated with asthma. One of the discovered genes related to asthma is ADAM33. However, the relationship between ADAM33 gene polymorphisms and asthma is controversial. The aim of this study was to investigate the association between four ADAM33 gene SNPs and susceptibility to asthma in patients from southwestern Iran. Materials and Methods: ADAM33 gene polymorphisms at positions T+1 (rs2280091), T1 (rs3918396), S1 (rs2280089), and F+1 (rs511898) were examined in 150 patients with asthma and 149 age- and sex-matched healthy controls with a PCR-RFLP method. Results: There were no differences between patients and controls in allelic or genotype frequencies of ADAM33 SNPs. We found no associations between allelic or genotype distribution of the SNPs and spirometry indices, concomitant involvement of other allergic diseases, or exposure to cigarette smoke. In contrast to H4 haplotype, which appeared to be protective against asthma, inheritance of H2 and H3 haplotypes increased the risk of asthma up to 2–3 folds. Conclusion: ADAM33 gene polymorphisms appear to play a partial role in asthma susceptibility, investigation of expression changes in this gene in response to environmental factors or the local formation of a soluble form of the molecule in the lung can be helpful to elucidate the impact of this molecule in the induction of asthma.

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. [ABSTRACT FROM AUTHOR]

Asthma is a multifactorial issue, principally coming about because of collaborations among hereditary and ecological variables. ADAM33 gene (situated on chromosome 20p13) has been accounted for to assume an imperative job in asthma. This survey article is proposed to incorporate the majority of the productions, until this point, which have evaluated the relationship of ADAM33 gene polymorphisms just as have demonstrated the job of ADAM33 gene in aviation route rebuilding and their demeanor with asthma. Our investigation on "ADAM33 gene and asthma, reveales "ADAM33 gene polymorphisms" at exon 19 G>C is related with asthma. The genotype dispersion of ADAM33 (rs528557) was significantly different on the off chance that and control (χ2 = 18.67, P<0.0001). HC group showed a significant increase in 'GG' genotype when contrasted with asthma patients (59.5% versus 39.44.0%). The heterozygous genotype 'GC' was fundamentally dispersed in HC group when contrasted with cases (34% in control versus 43.88% on the off chance that). Genotype 'TT' was available on the off chance that 16.6% and 6.5% in charge and significantly different. An odds ratio of 0.443 in separately for 'GG' genotype demonstrated a defensive impact of this regular genotype 'GG' in our populace. By and large allele 'G' was observed to be in altogether low frequency in asthma patients bunch when contrasted with HC gathering (61.38% versus 76.5%) while allele 'C' was available in higher frequency in the ailment gathering (χ2 =20.35, P<0.0001). G allele was discovered defensive with chances proportion of 0.4884 in the interim C allele demonstrates chances proportion 2.047 which shows its solid relationship with athma defenselessness. The example of genotype, allele distribution and carriage rate in ailment and control bunch recommended a critical relationship of ADAM33 (rs528557) (carriage of 'CC' and 'GC') in asthma susceptibility. [ABSTRACT FROM AUTHOR]

Abstract Polymorphisms in the gene encoding for A disintegrin and metalloprotease 33 (ADAM33) are closely associated with the risk of bronchial asthma attacks in different populations. We collected blood samples from 248 asthma patients – 130 of the Han ethnic group and 118 of the Mongolian ethnic group – living in the Inner Mongolia region of China, and analyzed the single nuclear polymorphisms (SNPs) of the T1, T2 and V4 loci of the ADAM33 gene using PCR-RFLP (restriction fragment length polymorphism). In addition, we also tested 256 healthy controls (134 and 122 from the Han and Mongolian ethnic groups respectively) for the same SNPs. Three genotypes of the T1, T2 and V4 loci were predominantly detected: while polymorphisms in the T1 locus were significantly associated with asthma risk in both Mongolian and Han ethnicities (P < 0.05, ∗P < 0.05), that in the V4 locus were relevant only in the Mongolian patients (P < 0.05, ∗P > 0.05). In contrast, polymorphisms in the T2 locus showed no significant association with asthma risk in either ethnic group (P > 0.05, ∗P > 0.05). [ABSTRACT FROM AUTHOR]

Objective(s): Asthma, the most frequent chronic respiratory disease, results from a complex interaction between multiple genes and environmental factors. To date, more than 100 candidate genes and single nucleotide polymorphisms (SNPs) have been reported to be associated with asthma. One of the discovered genes related to asthma is ADAM33. However, the relationship between ADAM33 gene polymorphisms and asthma is controversial. The aim of this study was to investigate the association between four ADAM33 gene SNPs and susceptibility to asthma in patients from southwestern Iran. Materials and Methods: ADAM33 gene polymorphisms at positions T+1 (rs2280091), T1 (rs3918396), S1 (rs2280089), and F+1 (rs511898) were examined in 150 patients with asthma and 149 age- and sex-matched healthy controls with a PCR-RFLP method. Results: There were no differences between patients and controls in allelic or genotype frequencies of ADAM33 SNPs. We found no associations between allelic or genotype distribution of the SNPs and spirometry indices, concomitant involvement of other allergic diseases, or exposure to cigarette smoke. In contrast to H4 haplotype, which appeared to be protective against asthma, inheritance of H2 and H3 haplotypes increased the risk of asthma up to 2-3 folds. Conclusion: ADAM33 gene polymorphisms appear to play a partial role in asthma susceptibility, investigation of expression changes in this gene in response to environmental factors or the local formation of a soluble form of the molecule in the lung can be helpful to elucidate the impact of this molecule in the induction of asthma. [ABSTRACT FROM AUTHOR]

Asthma, affecting a growing number of populations, is a clinical condition with complex cellular and genetic factors. Single nucleotide polymorphisms (SNPs) in gene coding for molecules, which play major roles in the immunopathogenesis of asthma have been considered recently as genetic predisposing factors this disease. Possible association between two SNPs in a disintegrin and metalloprotease 33 (ADAM33), which participates in airway remodeling, and susceptibility to asthma was studied in this study. 190 patients with asthma and 180 healthy controls were enrolled in this case-control study. Using conventional PCR method, specific bands were amplified and the frequency of genotypes of T1 (rs2280091) and V4 (rs2787094) ADAM33 SNPs were determined by digestion with NcoI and PstI, respectively. The results showed that the frequency of genotypes of T1 and V4 were not significantly different between patients and controls (p=0.54 and p=0.85, respectively). On the other hand, no significant differences were seen in allele frequency of both T1 and V4 SNPs (p=0.15 and p=0.47, respectively). In agreement with some other studies in different populations, our results showed no association between frequency of genotype or alleles of both T1 and V4 SNPs in ADAM33 gene and predisposition to asthma in Azerbaijan population of Iran. Genetic differences in different ethnic groups might be involved in such inconsistent results. More studies in populations with larger number of patients and healthy individuals are needed for concluding remarks for involvement of ADAM33 SNPs in asthma.

This study aimed to investigate the association between ADAM metallopeptidase domain 33 (ADAM33) gene polymorphisms and the risk of childhood asthma. The relevant studies about the relationship between ADAM33 gene polymorphisms and childhood asthma were searched from electronic databases and the deadline of retrieval was May 2016. The single nucleotide polymorphisms (SNPs) of ADAM33 (rs511898, rs2280092, rs3918396, rs528557, rs2853209, rs44707, rs2280091 and rs2280089) were analyzed based on several models including the allele, codominant, recessive and dominant models. The results showed that the ADAM33 rs2280091 polymorphism in all four genetic models was associated with an increased risk of childhood asthma. Positive associations were also found between the polymorphisms rs2280090, rs2787094, rs44707 and rs528557 and childhood asthma in some genetic models. This meta-analysis suggested that ADAM33 polymorphisms rs2280091, rs2280090, rs2787094, rs44707 and rs528557 were significantly associated with a high risk of childhood asthma.

Objective(s): Asthma results from the interaction between genetic and environmental factors. ADAM33 gene on chromosome 20p13 is associated with asthma and airway hyperresponsiveness. Materials and Methods: This is a case-control study, where four SNPs S1 (rs3918396), T1 (rs2280091), T2 (rs2280090), V4 (rs2787094) of ADAM33 gene have been assessed in patients with allergic asthma and normal controls (95 patients and 86 normal). Blood samples of these participants have been genotyped by PCR and the RFLP method. Results: There was no association between asthmatic patients and polymorphisms of alleles, genotypes and haplotypes of the ADAM33 gene. When categorizing the asthmatic patients in severe, moderate and mild groups, associations in the subcategories of asthmatic patients were found. There were associations between polymorphisms of C allele of T1 SNP with severe asthmatic patients and G allele of V4 SNP with moderate asthmatics respectively (P=0.006, P=0.01). There was a significant association between sensitivity to mite and polymorphism of C allele of T1 SNP (P=0.02). Besides, there was a significant association between sensitivity to weeds and genotype GG of V4 SNP (P=0.05). Conclusion: Polymorphisms of ADAM33 gene might be associated with severe asthma and sensitivity to aeroallergens in northeast of Iran, but further studies are needed to determine the polymorphisms in this area and other regions of our country.

Objective: To study the association between ADAM33 and keloid scars in the northeastern Chinese population. Methods: A total of 283 keloid scar patients and a control group of 290 healthy volunteers were recruited for this study. Six polymorphic loci (V4, T+1, T2, T1, S2 and Q-1 ) of ADAM33 were selected for genotyping. Genotypes were determined by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: We observed the frequency of the rs612709 A allele exhibited a significantly decreased frequency in cases than in controls(22 vs.39.6%, PP= 0.041). In contrast, the haplotype H8 (GGGAGG) was more common in the control group than in the case group (P=0.022). Conclusions: Our data suggest that the ADAM33 polymorphisms may be associated with keloid scars in the northeastern Chinese population.

Asthma, affecting a growing number of populations, is a clinical condition with complex cellular and genetic factors. Single nucleotide polymorphisms (SNPs) in gene coding for molecules, which play major roles in the immunopathogenesis of asthma have been considered recently as genetic predisposing factors this disease. Possible association between two SNPs in a disintegrin and metalloprotease 33 (ADAM33), which participates in airway remodeling, and susceptibility to asthma was studied in this study. 190 patients with asthma and 180 healthy controls were enrolled in this case-control study. Using conventional PCR method, specific bands were amplified and the frequency of genotypes of T1 (rs2280091) and V4 (rs2787094) ADAM33 SNPs were determined by digestion with NcoI and PstI, respectively. The results showed that the frequency of genotypes of T1 and V4 were not significantly different between patients and controls (p=0.54 and p=0.85, respectively). On the other hand, no significant differences were seen in allele frequency of both T1 and V4 SNPs (p=0.15 and p=0.47, respectively). In agreement with some other studies in different populations, our results showed no association between frequency of genotype or alleles of both T1 and V4 SNPs in ADAM33 gene and predisposition to asthma in Azerbaijan population of Iran. Genetic differences in different ethnic groups might be involved in such inconsistent results. More studies in populations with larger number of patients and healthy individuals are needed for concluding remarks for involvement of ADAM33 SNPs in asthma. [ABSTRACT FROM AUTHOR]

Objective: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Astma jest przewlekłą chorobą płuc, której głównymi cechami są odwracalna obturacja oskrzeli, zapalenie i nadreaktywność dróg oddechowych. Ostatnia z nich, określana jako nadmierna skurczowa odpowiedź oskrzeli na nieswoiste substancje drażniące, jest najbardziej charakterystyczna dla astmy i stwierdza się ją u wszystkich dzieci z czynną chorobą i większości tych aktualnie bez objawów, ale z wywiadem astmy w przeszłości. Rzeczywisty mechanizm nadreaktywności oskrzeli (NO) w astmie, także dziecięcej, pozostaje niejasny. Powszechnie sądzi się, że NO jest skutkiem przewlekłego zapalenia oskrzeli. Potwierdzają to obserwacje dotyczące wzrostu NO po ekspozycji na alergeny i jej zmniejszenia się pod wpływem leczenia przeciwzapalnego. Jednak brak korelacji między NO a wykładnikami stanu zapalnego w astmie sugeruje udział także innych, niezapalnych mechanizmów patogenetycznych NO. Zarówno badania rodzin, jak i bliźniąt z astmą wskazują na silne genetyczne uwarunkowania NO. W badaniach u ludzi i myszy zidentyfikowano więcej niż jeden obszar genowy związany z astmą i charakteryzującymi ją fenotypami, w tym NO. Istotną rolę odgrywa także związana z zapaleniem strukturalna przebudowa ściany oskrzeli. Artykuł stanowi przegląd możliwych mechanizmów wywołujących NO, które zostały omówione w literaturze medycznej. Wykazano, że nieswoista NO jest zjawiskiem wieloczynnikowym, o złożonej i wciąż niedostatecznie poznanej patogenezie.

Abstract Study objective The pathogenesis of chronic obstructive pulmonary disease (COPD) is characterized by an interaction of environmental influences, particularly cigarette smoking, and genetic determinants. Given the global increase in COPD, research on the genomic variants that affect susceptibility to this complex disorder is reviving. In the present study, we investigated whether single nucleotide polymorphisms in 'a disinter-grin and metalloprotease' 33 (ADAM33) are associated with the development and course of COPD. Patients and design We genotyped 150 German COPD patients and 152 healthy controls for the presence of the F+1 and S_2 SNPs in ADAM 33 that lead to the base pair exchange G to A and C to G, respectively. To assess whether these genetic variants are influential in the course of COPD, we subdivided the cohort into two subgroups comprising 60 patients with a stable and 90 patients with an unstable course of disease. Results In ADAM33, the frequency of the F+1 A allele was 35.0% among stable and 43.9% among unstable COPD subjects, which was not significantly different from the 35.5% found in the controls (P = 0.92 and P = 0.07, respectively). The frequency of the S_2 mutant allele in subjects with a stable COPD was 23.3% (P = 0.32), in subjects with an unstable course 30.6% (P = 0.47). Conclusion The study shows that there is no significant difference in the distribution of the tested SNPs between subjects with and without COPD. Furthermore, these polymorphisms appear to have no consequences for the stability of the disease course.

Asthma and COPD are complex diseases with strong genetic and environmental components. These common pulmonary diseases have both different and similar clinical features. Molecular genetic techniques are being used to improve understanding of these common late onset disorders. Recently, several genes and genetic loci associated with increased susceptibility to asthma and COPD have been described. Many of these genes are expressed in the lung tissues, indicating that events in lung tissues might drive disease processes. Lung tissues are rich sources of innate danger signals, and an increased understanding of how the lung tissues communicate with the immune system to maintain healthy tissue might provide new insights into the pathogenesis of chronic inflammatory lung diseases in which injury and repair are in disequilibrium. Given that the innate immune system is at the interface between the airways and environmental insults, genetic polymorphisms in genes related to the innate immune system are likely to affect susceptibility to both asthma and CopD. In addition, some findings from genetic studies provide molecular support for the point of view proposed in the Dutch hypothesis regarding the relationship between asthma and COPD, which highlights the complexity of the pathways that can induce small airway disease and suggests that there is a continuum between asthma and COPD.

OBJETIVO: Verificar, em uma amostra de pacientes com asma atópica persistente leve, moderada e grave, a associação entre os polimorfismos dos genes fator de crescimento transformante-beta1 (TGF-beta1) (C-509T e T869C), CD14 (C-159T), IL-4 (C-590T), IL-4R (ILe50Val) e ADAM33 (S_2) com a gravidade da asma. MÉTODOS: Realizou-se um estudo clínico laboratorial prospectivo em pacientes com asma atópica persistente, comparados a um grupo controle no Hospital Universitário da Universidade Estadual de Campinas nos anos de 2006 e 2007. A análise do polimorfismo T869C do gene TGF-beta1 foi realizada pela técnica de reação em cadeia da polimerase (PCR) + sistema de amplificação refratária de mutação (ARMS). Os outros polimorfismos, C-509T do gene TGF-beta1, C-159T do gene CD14, C-590T da IL-4, ILe50Val da IL-4Ra e S2 do gene ADAM33, foram detectados por PCR e enzima de restrição. RESULTADOS: Foram incluídos 88 pacientes com asma atópica persistente (27 leves, 23 moderados e 38 graves) e 202 indivíduos saudáveis, doadores de sangue. Em relação ao polimorfismo T869C (TGF-beta1), observou-se uma associação entre o genótipo CC e os pacientes com asma grave. Nenhuma associação foi encontrada com os polimorfismos C-509T (TGF-beta1), C-590T (IL4) e S_2 (ADAM33). Quando se comparou a distribuição da freqüência genotípica do polimorfismo C-159T (CD14) na asma grave com o grupo controle, foi observado um resultado significativo com o genótipo TT. Houve associação significativa do genótipo Val/Val (IL-4R) com a asma leve. CONCLUSÃO: Nossos resultados indicam que os polimorfismos T869C (TGF-beta1), C-159T (CD14) e Val/Val (IL-4R) podem estar envolvidos na modulação da gravidade da asma.OBJECTIVE: To verify the association of transforming growth factor-beta1 (TGF-beta1) (C-509T and T869C), CD14 (C-159T), IL-4 (C-590T), IL-4R (ILe50Val) and ADAM33 (S_2) gene polymorphisms with asthma severity in a sample of patients with mild, moderate and severe persistent atopic asthma. METHODS: A clinical, laboratory, prospective study was performed in patients with persistent atopic asthma, compared to a control group at Hospital Universitário da Universidade Estadual de Campinas between 2006 and 2007. Analysis of the TGF-beta1 T869C gene polymorphism was performed using the technique polymerase chain reaction (PCR) + amplification refractory mutation system (ARMS). TGF-beta1 C-509T, CD14 C-159T, IL-4 C-590T, IL-4Ra ILe50Val, and ADAM33 S2 gene polymorphisms were detected by PCR and restriction enzyme. RESULTS: This study included 88 patients with persistent atopic asthma (27 mild, 23 moderate and 38 severe) and 202 healthy blood donors. As to T869C polymorphism (TGF-beta1), there was an association between the CC genotype and patients with severe asthma. There was no association in polymorphisms C-509T (TGF-beta1), C-590T (IL-4) and S_2 (ADAM33). When distribution of C-159T polymorphism genotype frequency (CD14) in severe asthma was compared with the control group, there was a significant result with the TT genotype. There was significant association of the Val/Val genotype (IL-4R) with mild asthma. CONCLUSION: Our results indicate that T869C (TGF-beta1), C-159T (CD14) and Val/Val (IL-4R) polymorphisms might be involved in modulation of asthma severity.

Background: Asthma is a chronic respiratory disease characterized by reversible airway obstruction with persistent airway inflammation and airway remodeling, which is associated with increased airway smooth muscle (ASM) mass. Vascular endothelial growth factor (VEGF) has been implicated in inflammatory and airway blood vessel remodeling in asthma. Recent evidence indicates that a deficiency of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) may influence asthma pathogenesis. A disintegrin and metalloproteinase (ADAM)33 has been identified as playing a role in the pathophysiology of asthma. ADAM33, which is expressed in ASM cells, is suggested to play a role in the function of these cells. Recent studies show that 1,25-(OH)2D3 exerts direct inhibitory effects on passively sensitized human ASM cells in vitro, including inhibition of ADAM33 expression and cell proliferation; however, the mechanism has not been fully understood.Methods: In order to elucidate the precise mechanism underlying the effect of 1,25(OH)2D3 on VEGF-induced ADAM33 expression and ASM cell proliferation, we tested the effects of 1,25(OH)2D3 on cell cycle progression and evaluated the levels of phospho-VEGF receptor 2 (VEGFR2), phospho-extracellular signal-regulated kinase 1/2 (ERK1/2), and phospho-Akt in VEGF-stimulated ASM cells.Results: We found that 1,25(OH)2D3 inhibited VEGF-induced ADAM33 expression and ASM cell proliferation, as well as cell cycle arrest. Additionally, VEGF-induced ADAM33 expression and ASM cell proliferation was suppressed via inhibition of ERK1/2 activity, but not that of Akt. Furthermore, 1,25(OH)2D3 treatment inhibited VEGF-induced activation of VEGFR2 as well as that of ERK and Akt in a concentration-dependent manner. 1,25(OH)2D3 also inhibited transforming growth factor (TGF)-β-induced VEGF secretion by ASM cells.Conclusions: Collectively, our findings suggest that 1,25(OH)2D3 inhibits VEGF-induced ASM cell proliferation by suppressing VEGFR2 and ERK1/2 activation and downregulating ADAM33. Further studies of these mechanisms are needed to facilitate the development of treatments for smooth muscle hyperplasia-associated diseases of the airway such as asthma. [ABSTRACT FROM AUTHOR]

Background: Many studies have attempted to identify gene-gene interactions affecting asthma susceptibility. However, these studies have typically used candidate gene approaches in limiting the genetic search space, and there have been few searches for gene-gene interactions on a genome-wide scale. We aimed to conduct a genome-wide gene-gene interaction study for asthma, using data from the GABRIEL Consortium. Results: A two-stage study design was used, including a screening analysis (N = 1625 subjects) and a follow-up analysis (N = 5264 subjects). In the screening analysis, all pairwise interactions among 301,547 SNPs were evaluated, encompassing a total of 4.55 × 1010 interactions. Those with a screening interaction p-value < 10-5 were evaluated in the follow-up analysis. No interaction selected from the screening analysis met strict statistical significance in the follow-up (p-value < 1.45 × 10-7). However, the top-ranked interaction (rs910652 [20p13] × rs11684871 [2q14]) in the follow-up (p-value = 1.58 × 10-6) was significant in one component of a replication analysis. This interaction was notable in that rs910652 is located within 78 kilobases of ADAM33, which is one of the most well studied asthma susceptibility genes. In addition, rs11684871 is located in or near GLI2, which may have biologically relevant roles in asthma. Conclusions: Using a genome-wide approach, we identified and found suggestive evidence of replication for a gene-gene interaction in asthma involving loci that are potentially highly relevant in asthma pathogenesis. [ABSTRACT FROM AUTHOR]

Objective To investigate the correlation between ADAM33 T1， S2 gene polymorphism and Bronchial asthma risk in china. Methods We retrived the relevant published studies about ADAM33 T1，S2 gene polymorphism and bronchial asthma risk. Then we divided the population into Chinese and other Asian population. Odds ratio （OR）of Case group and control group was selected as the effect index. Stata 11.0 software was used to calculate heterogeneity test，ORs and 95% CI of two areas，and gave the forest plot and funnel plot of meta results. Results A total of 27 studies were included in this analysis，18 studies in ADAM33 T1 site were 3881 cases in case group， and 3780 cases in control group; and 14 studies in ADAM33 S2 site were 3222 cases in case group，and 3513 cases in control group. Additive model，dominant model，recessive model of ADAM33 T1 in Chinese had association with the susceptibility of bronchial asthma. The results were OR=1.488，95% CI：1.002-2.167 in Additive model， OR=1.619，95% CI：1.059-2.475 in dominant model；OR=2.523，95% CI：1.910-3.333 in recessive model. Three models of ADAM33 T1 in other Asian country had no association with the susceptibility of Bronchial Asthma. Three gene model of ADAM33 S2 in Asian had no association with bronchial asthma susceptibility. Except ADAM33 T1 polymorphism in recessive model， other mode of T1， S2 had no publication bias in Chinese population. Conclusion There are association between ADAM33 T1 gene polymorphism and bronchial asthma， but ADAM33 S2 gene polymorphism and bronchial asthma have no association in Chinese population. [ABSTRACT FROM AUTHOR]

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 (Allelep = 0.0189, Genotypep = 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. [ABSTRACT FROM PUBLISHER]

Objective: Asthma is a common childhood disease with strong genetic components. This study compared whole-genome expression differences between asthmatic young children and healthy controls to identify gene signatures of childhood asthma. Methods: Total RNA extracted from peripheral blood mononuclear cells (PBMC) was subjected to microarray analysis. QRT-PCR was performed to verify the microarray results. Classification and functional characterization of differential genes were illustrated by hierarchical clustering and gene ontology analysis. Multiple logistic regression (MLR) analysis, receiver operating characteristic (ROC) curve analysis, and discriminate power were used to scan asthma-specific diagnostic markers. Results: For foldchange42 and p50.05, there were 758 named differential genes. The results of QRT-PCR confirmed successfully the array data. Hierarchical clustering divided 29 highly possible genes into seven categories and the genes in the same cluster were likely to possess similar expression patterns or functions. Gene ontology analysis presented that differential genes primarily enriched in immune response, response to stress or stimulus, and regulation of apoptosis in biological process. MLR and ROC curve analysis revealed that the combination of ADAM33, Smad7, and LIGHT possessed excellent discriminating power. Conclusions: The combination of ADAM33, Smad7, and LIGHT would be a reliable and useful childhood asthma model for prediction and diagnosis. [ABSTRACT FROM AUTHOR]

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 = 94 %; G vs. A, OR 1.53, 95 % CI 1.32-1.78, I = 94 %), T2 (GA+AA vs. GG, OR 1.26, 95 % CI 1.06-1.51, I = 92 %; G vs. A, OR 1.27, 95 % CI 1.08-1.50, I = 92 %), V4 (CG+GG vs. CC OR 1.35, 95 % CI 1.14-1.59, I = 95 %;G vs. C OR 1.28, 95 % CI 1.13-1.44, I = 96 %) and Q−1 (GA+AA vs. GG OR 1.55, 95 % CI 1.24-1.95, I = 74 %; G vs. C OR 1.46, 95 % CI 1.19-1.79, I = 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. [ABSTRACT FROM AUTHOR]

Background ADAM28, ADAM33, IL-13, IL-4 and other cytokines (IL-6 and IL-10) seem to play important roles in the persistence and maintenance of acute inflammatory processes that ultimately lead to lung remodeling and pulmonary fibrosis, which may be responsible for the high morbidity and mortality rates associated with non-pandemic acute viral pneumonias in childhood. Objectives The aim of this study was to evaluate the roles of ADAM33, ADAM28, IL4, IL6, IL10 and IL13 in the development of inflammation and alveolar fibrosis due to lethal acute respiratory infections of the lower airway in a pediatric population, especially in those with viral etiology. Study design For this study, 193 cases were selected, and samples from the cases were processed for viral antigen detection by immunohistochemistry and then separated into two groups: virus-positive ( n = 68) and virus-negative ( n = 125). Immunohistochemistry was performed to assess the presence of metalloproteinases (ADAM33 and ADAM28) and inflammatory cytokines (IL-4, IL-13, IL-6, IL-10) in the alveolar septa. Results The virus-positive group showed stronger immunolabeling for ADAM33, ADAM28, IL-4 and IL-13 ( p < 0.0001 for all variables). The staining intensities for ADAM33 and ADAM28 were directly proportional to the intensities for IL-4 and IL-13 ( p < 0.0001). Conclusions The results of this study suggest that these proteins play important roles in pulmonary inflammatory reactions elicited against etiological viral agents. In addition, these mediators may affect the process of lung remodeling and the development of pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Objective(s): Asthma results from the interaction between genetic and environmental factors. ADAM33 gene on chromosome 20p13 is associated with asthma and airway hyperresponsiveness. Materials and Methods: This is a case-control study, where four SNPs S1 (rs3918396), T1 (rs2280091), T2 (rs2280090), V4 (rs2787094) of ADAM33 gene have been assessed in patients with allergic asthma and normal controls (95 patients and 86 normal). Blood samples of these participants have been genotyped by PCR and the RFLP method. Results: There was no association between asthmatic patients and polymorphisms of alleles, genotypes and haplotypes of the ADAM33 gene. When categorizing the asthmatic patients in severe, moderate and mild groups, associations in the subcategories of asthmatic patients were found. There were associations between polymorphisms of C allele of T1 SNP with severe asthmatic patients and G allele of V4 SNP with moderate asthmatics respectively (P=0.006, P=0.01). There was a significant association between sensitivity to mite and polymorphism of C allele of T1 SNP (P=0.02). Besides, there was a significant association between sensitivity to weeds and genotype GG of V4 SNP (P=0.05). Conclusion: Polymorphisms of ADAM33 gene might be associated with severe asthma and sensitivity to aeroallergens in northeast of Iran, but further studies are needed to determine the polymorphisms in this area and other regions of our country. [ABSTRACT FROM AUTHOR]

Objective: To study the association between ADAM33 and keloid scars in the northeastern Chinese population. Methods: A total of 283 keloid scar patients and a control group of 290 healthy volunteers were recruited for this study. Six polymorphic loci (V4, T+1, T2, T1, S2 and Q-1 ) of ADAM33 were selected for genotyping. Genotypes were determined by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: We observed the frequency of the rs612709 A allele exhibited a significantly decreased frequency in cases than in controls(22 vs.39.6%, P<0.0001) We also found that the frequencies of H2 (GGAAGA) haplotypes was significantly higher in the case group than in the control group (P= 0.041). In contrast, the haplotype H8 (GGGAGG) was more common in the control group than in the case group (P=0.022). Conclusions: Our data suggest that the ADAM33 polymorphisms may be associated with keloid scars in the northeastern Chinese population. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The aim of the present study was to explore the associations of genetic variants in the ADAM33 and TGF-β1 genes with the risk of childhood asthma. A total of 299 asthmatic children and 311 healthy controls were recruited in the hospital-based case-control study. The asthmatic subjects were further divided into mild and severe groups according to disease severity. Single-nucleotide polymorphisms (SNP) at ADAM33 V4, T2, S2 and T1, and TGF-β1 C-509T and T869C were selected and detected with PCR-RFLP. The associations of the SNPs with asthma risk and severity were analyzed. The associations between the haplotypes of ADAM33 and TGF-β1 were also evaluated. Compared with the GG genotype, the GC and CC genotypes at V4 were associated with an increased asthma risk in children and the ORs were 2.92 and 10.56, respectively. Compared with the CC genotype, the CT/TT genotype at C-509T was associated with an increased asthma risk and the OR was 2.26. Subsequent to stratification by asthma severity, compared with the V4 GG genotype, it was found that the CG and CC genotypes were associated with a mild asthma risk and the ORs were 3.00 and 5.99, respectively. The SNP at C-509T (CT/TT vs. CC) was associated with mild asthma (OR = 2.34), whereas a marginally significant association was detected between the SNP (CT/ TT vs. CC) and severe asthma risk (OR = 2.19). The haplotype analysis revealed that, compared with the GGCA haplotype of ADAM33, significant associations of the haplotypes of CGCG, CGGA, GACA, GACG and GAGA with asthma risk were observed, and the ORs were 31.12, 12.24, 4.73, 30.85 and 4.83, respectively. No significant association was detected between the TGF-β1 haplotypes and asthma risk. The genetic variants at V4 and C-509T had the potential to modify the childhood asthma risk and the associations showed no notable difference with the disease severity. Thus, ADAM33 haplotypes provided more useful information in the prediction of asthma risk. [ABSTRACT FROM AUTHOR]

Background: Genetic factors play a role in the development and severity of chronic obstructive pulmonary disease (COPD). The pathogenesis of COPD is a multifactorial process including an inflammatory cell profile. Recent studies revealed that single nucleotide polymorphisms (SNPs) within ADAM33 increased the susceptibility to COPD through changing the airway inflammatory process and lung function. Methods: In this paper, we investigated associations of four polymorphisms (T1, T2, S2 and Q-1) of ADAM33 as well as their haplotypes with pulmonary function and airway inflammatory process in an East Asian population of patients with COPD. Results: We found that T1, T2 and Q-1 were significantly associated with the changes of pulmonary function and components of cells in sputum of COPD, and T1 and Q-1 were significantly associated with cytokines and mediators of inflammation in airway of COPD in recessive models. 10 haplotypes were significantly associated with transfer factor of the lung for carbon monoxide in the disease state, 4 haplotypes were significantly associated with forced expiratory volume in one second, and other haplotypes were associated with airway inflammation. Conclusions: We confirmed for the first time that ADAM33 was involved in the pathogenesis of COPD by affecting airway inflammation and immune response in an East Asian population. Our results made the genetic background of COPD, a common and disabling disease, more apparent, which would supply genetic support for the study of the mechanism, classification and treatment for this disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]