Association of a Disintegrin and Metalloproteinase33 Gene Polymorphisms with Chronic ObstructivePulmonary Disease in Iraqi Population

Chronic obstructive pulmonary disease (COPD) is predisposed by environmental and hereditary factors”. A disintegrin and metalloproteinase 33 gene (ADAM33) has been one of the most stimulating gene for asthma since of their first association withthe disease in Caucasian population". "Recently,ADAM33 was shown to be associated with decrease of lung function andCOPD. The target of this study was to evaluate the potential correlation between polymorphisms of ADAM33 and COPD in Iraqi" population. This study included,400 cases of COPD and 400 healthy individuals as control group.“Two polymorphic loci (V4 and Q-1) of ADAM33 were selected for genotyping that determined by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. “Statistically significant distinctions in the distribution of the wild and mutant genotypes between patients and control. In addition,significant association (P <0. 0001) between COPD and mutant genotypes (V4/GG and Q-1/AA) are detected.The results of this study designate that ADAM33/V1 and Q-1 polymorphisms is a hazard factor for COPD among Iraqi society.


INTRODUCTION
Chronic("obstructive pulmonary disease is characterized by the development of airflow limitation that is progressive and not completely reversible [1,19], and is a major and growing public health burden as the 4 th leading cause of loss of life in the world regarding to 2002 statistics [2]. Chronic obstructive pulmonary disease is estimated to be one of the main five chronic diseases in terms of global mortality and morbidity by 2030 [3]. The relationship between gene polymorphisms and COPD susceptibility has recently been paid special attention and was explored in a large number of studies on hundreds of genes, however the results varied between studies and populations of people") [8]. ("Multiple genes have been found for asthma and COPD. In addition to genes unique to these diseases, some shared genetic risk factors exist. Moreover, there are common host risk factors and environmental risk factors for asthma and COPD. Based on the data available, some studies put forward that genes that affect lung development in utero and lung growth in early childhood in interaction with environmental detrimental stimuli, such as smoking and air pollution, are contributing to asthma in childhood and the ultimate development of COPD [16]. A disintegrin and metalloproteinase 33 gene, belonging to the disintegrin and metalloprotease family, plays a vital role in cell adhesion, proliferation, difference, signaling, apoptosis, and other responses [4,20]. van Eerdewegh et al., (2002) found a relationship between the ADAM33 gene with") ("asthma and bronchial hyper responsiveness. In the past decade, an increasing number of studies have shown associations between ADAM33 polymorphisms and asthma susceptibility, as well as other pulmonary diseases in several populations [5,6,7,15]. van Diemen et al., (2005) reported, for the first time, that single nucleotide polymorphisms (SNPs) in ADAM33 were associated with accelerated lung. The present study is the first attempt to detect the association between ADAM33/V4 and Q-1 polymorphisms and COPD in")Iraqi population.

MATERIAL AND METHODS Study design:
The current study was conducted on 400 patients (237males, 163 females) their ages from 30-80 year were seen in Al-Diwaniya Teaching Hospital. The patients were diagnosed clinically by physician as having COPD. The diagnosis of COPD performed by using special criteria or standards: {1} record of cigarette smoking (at least for 9 years ago)("in patients who were current smokers at the time of evaluation {2} not exposition to other substances that identified to cause lung abnormalities {3} nonexistence of atopy {4} no history of systemic or other pulmonary disease or congenital and /or acquired systemic immunodeficiency {5}forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) <70% and FEV1 after inhalation of 200 mg salbutamol <80% ") [9]. Another group consist of 400 apparently healthy individuals (210 males and 190 female) their ages from 30-80 year without smoking or any history of systemic disease were clinically considered as a control group.
Molecular study: genomic DNA was extracted from blood " according to manufacturers' instructions of Genomic

RESULTS
The presence of family history is an important contributory factor in COPD. This study showed 260 (65%) of COPD patients have positive family history, Figure (
CONCLUSION COPD not causes by smoking or other environmental factors only but also strongly associated with genetic polymorphism. ADAM33/V4 and Q-1 SNP polymorphisms significantly correlated with COPD patients and this mean that individual who has ADAM33/V4 and Q-1 SNP polymorphisms more susceptible to COPD in this") population.