TNF‐α‐, TNF‐β‐, IL‐6‐, and IL‐10‐promoter polymorphisms in patients with chronic obstructive pulmonary disease

Abstract

Chronic obstructive pulmonary disease (COPD) is a major health problem. The disease is driven by abnormal inflammatory reactions in response to inhaled particles and fumes. Therefore, inflammatory mediators are postulated to be of distinct importance. In the present case-control study, we investigated interleukin (IL)-promoter polymorphisms known to correlate with altered transcription levels of their gene products in patients with COPD. We analyzed tumor necrosis factor-alpha (TNF-alpha)-308, TNF-beta-intron1-252, IL-6-174, IL-10-819, and IL-10-1082 polymorphisms in 469 individuals using restriction fragment length polymorphism-based converted polymerase chain reaction. The study population consisted of 113 patients with COPD based on chronic bronchitis, divided into subgroups by severity (I degrees -III degrees ), 113 matched hospitalized individuals suffering from severe coronary heart disease without pulmonary disease (age-, sex-, and smoking-matched control group), and 243 healthy individuals (population control group). The matched analysis showed no significant differences in genotype distribution of all tested polymorphisms between the matched controls and the COPD patients. However, comparison with the population controls revealed significant differences in IL-10-1082 A/G genotype frequencies (P = 0.0247 for the whole COPD group, P = 0.009 for smokers only), with the genotypes carrying the G allele more common in the COPD cases [odds ratio (OR) = 1.66, 95% confidence interval (CI) 1.01-2.75; P = 0.046]. Interestingly, this shift toward more G alleles was even more pronounced in the matched control group (OR = 2.55, 95% CI 1.47-4.41; P = 0.0007), suggesting both presented groups share corresponding underlying mechanisms. The IL-10-1082_G allele is known to correlate with altered IL-10 levels. Therefore, it might be associated with altered or abnormal inflammatory response, a mechanism that could be postulated to be important in both chronic bronchitis and coronary heart disease.

Intestinal inflammation-induced growth retardation acts through IL-6 in rats and depends on the –174 IL-6 G/C polymorphism in children

“…Although it has been speculated that there may be a potential glucocorticoid receptor at position Ϫ557 to Ϫ552, the sequence around the Ϫ572 site does not have a strong homology to any known transcriptional factor binding site. Thus, these observations, together with the wealth of IL-6 Ϫ174 genotype-association studies (45)(46)(47)(48)(49)(50), indicate that, in Northern Europeans, the IL-6 Ϫ174 genotype is probably the main promoter polymorphism determining variation in IL-6 induction.…”

Avaliação de polimorfismo de nucleotídeo único em gene promotor da citocina inflamatória IL6 quanto à susceptibilidade em doenças pulmonares

“…Além da influência do alelo G à função pulmonar, Attaran et al (2010) ressaltam que a IL6 também acelera a libertação de proteínas de fase aguda de resposta inflamatória e piora a condição inflamatória subjacente. Para os sujeitos do grupo CP nossos achados corroboram com os estudos de Seifart et al (2005), o qual também observou maior prevalência do genótipo heterozigoto nos casos em uma população alemã, bem como os resultados apresentados por Colakogullari et al (2008) em um estudo turco. Sabe-se que o polimorfismo estudado no gene que codifica a IL6 está estritamente relacionado com a propensão a doença, além disso, o alelo dito de risco é responsável por aumentar a produção destas citocinas associando-as a processos inflamatórios, um fator na promoção da carcinogênese (ZHOU et al, 2015;JIA et al, 2015).…”

Association of the CYP1A1 MspI and TNFα-308 polymorphisms with chronic obstructive pulmonary disease in Inner Mongolia

“…Studies in Taiwanese (Huang et al, 1997), Japanese (Sakao et al, 2001), and Caucasian smokers (Gingo et al, 2008) showed similar results to those of the present study in demonstrating that the TNFα-308 polymorphism is a risk factor of COPD. However, studies in Thai (Chierakul et al, 2005), adenovirus C-infected Egyptian (Ezzeldin et al, 2012), Caucasian (Higham et al, 2000;Chappell et al, 2007), German (Seifart et al, 2005), and European-descended American (Tanaka et al, 2007) subjects showed opposite results. Teramoto et al (2008) stated that the TNFα-308 polymorphism was not associated with susceptibility to Asian COPD.…”

“…A common guanine (G) to adenine (A) substitution at position 308 in the TNFα gene promoter (rs1800629) increases gene transcriptional activity (Wilson et al, 1997;Wu and McClain, 1997). This polymorphism has been studied with respect to COPD in several populations, again producing contradictory results (Higham et al, 2000;Sakao et al, 2001;Seifart et al, 2005;Brøgger et al, 2006;Chappell et al, 2007).…”