Asthma is a complex inflammatory condition often associated with bronchial hyperreactivity and atopy. Genetic and environmental factors are implicated and several candidate genes have been implicated. Of these, the chemokine RANTES is responsible for the recruitment of inflammatory cells such as eosinophils and T-lymphocytes. We have recently identified a polymorphism within the RANTES promoter (−403 G →A) and have examined its role, using a PCR-RFLP assay, in the development of atopy and asthma in 201 Caucasian subjects. Atopic status was determined using skin prick testing and serum IgE levels. Severity of airway dysfunction was assessed using spirometric measurement (FEV 1 ) and methacholine challenge (PC 20 ). The −403 A allele was associated with an increased susceptibility to both atopy and asthma. Thus, the proportion of subjects carrying this allele was higher in each of atopic non-asthmatics, nonatopic asthmatics and atopic asthmatics compared with non-atopic, non-asthmatic controls. In particular, this allele was associated with skin test positivity but not IgE level. Homozygosity for the −403 A allele conferred a 6.5-fold increased risk of moderate/severe airway obstruction (FEV 1 р80% predicted), a marker for established asthma. Our data, whilst preliminary, indicate that the association of RANTES genotype with both atopy and asthma reflect independent effects, suggesting different mechanisms for the role of this chemokine in atopy and development of airway obstruction. Genes and Immunity (2000) 1, 509-514.
The aim of this study was to investigate whether polymorphisms in the tumor necrosis factor (TNF) and HLA-DRB1 gene regions are independently associated with rheumatoid arthritis (RA) in a population from Lugo region of northwestern Spain. RA patients (n=179) attending hospital outpatient clinics in Lugo, northwestern Spain and matched controls (n=145) were recruited. RA susceptibility in this population was predominantly associated with DRB1*0401, while erosive disease was associated with HLA-DRB1*0101 and DRB1*04. The increase in DRB1*04 was accounted for by an increase in DRB1*0404 and *0405 but not *0401 frequencies. In contrast, *0401 frequency was significantly increased in seropositive patients. The rheumatoid arthritis shared epitope (SE) was associated with increased risk for seropositive and erosive disease and this appeared to operate in a dose-dependent manner. Logistic regression analyses revealed that the TNF microsatellite markers TNFc1 and b3 were associated with RA independently of DRB1*04 and the SE. Carriage of a TNF c1 allele provided an increased risk of RA in SE-negative and SE-heterozygous individuals. TNFc1 and TNFb3 were not associated with erosive or seropositive disease. In contrast, TNF a2 was significantly associated with erosive disease which was independent of DRB1*04 and the SE. Further studies will be needed to establish why (TNFc1) polymorphism seemingly associated with low TNFalpha production, is a risk factor for RA.
CONTEXT:Matrix metalloproteinases (MMPs) are a family of enzymes that degrade various components of the extracellular matrix and are involved in the development and progression of cancer. Lung cancer is the most commonly diagnosed cancer in Lebanon. MMP1 is responsible for degrading stromal collagens, which enhance the ability of neoplastic cells to cross basal membrane of both the endothelium and the vascular endothelium. A recent meta-analysis has suggested that the MMP1-1607 2G allele may be associated with an increased risk for certain types of cancers.AIM:This study was undertaken to investigate the association between guanine insertion polymorphism in the MMP1 promoter and the susceptibility to lung cancer in the Lebanese population.SETTINGS AND DESIGN:This case-control study was conducted on 41 patients with lung cancer and 51 age-matched healthy controls, recruited from different regions of Lebanon.METHODS:Cases were histologically confirmed lung cancer patients obtained from different hospitals in Lebanon. Controls were healthy unrelated individuals with no history of cancer or genetic diseases. All subjects were genotyped for MMP1 -1607(1G>2G) polymorphism using polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP).RESULTS:No statistically significant differences were found when genotype and allele distribution of MMP1 -1607(1G>2G) polymorphism were compared between patients with lung cancer and controls [P= 0.6 by chi-squared test on a 3×2 contingency table; allelic P=0.61, OR (95% CI) = 1.18 (0.60-2.31)].CONCLUSION:Our data shows that MMP1 promoter polymorphism is not associated with lung cancer susceptibility in the Lebanese population.
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