Biomedical Engineering Reference
In-Depth Information
Recently, this association was confirmed by Sakao et al. (127) in a Japanese
population. In this study, 106 patients were selected on the basis of an
FEV
1
<
80% and an FEV
1
=
FVC
<
80%, and these individuals were com-
pared with 110 asymptomatic smokers or exsmokers and 129 adult blood
donors. The presence of the TNF
a
-308A allele (homozygotes and heterozy-
gotes combined) was significantly increased in cases (27%) compared with
both control groups (12%) yielding an OR of 2.6. Evidence for the role of
the TNF
a
-308A allele in the pathogenesis of COPD was further strength-
ened by the observation that this allele was associated with more severe
emphysema, as judged by high resolution CT (128).
In contrast, no association of the -308A allele with COPD was found
in a study of 53 physician diagnosed COPD patients and 65 controls from
the Japanese population (129). However, the sample size in this study was
small and there were considerably fewer subjects (2%) with the -308A allele
than in the study by Sakao et al. (127). Studies of Caucasian populations
have found no association of TNF
a
-308A with COPD (130) or rate of
decline of lung function (58). In a recent study in Caucasians from Italy,
the authors used ''moderate-to-severe COPD associated with emphysema''
as narrower criterion for the COPD phenotype and investigated its associa-
tion with the polymorphisms in TNF family genes (131). The results sug-
gested that none of these genes was a major genetic risk factor for COPD.
Interestingly, a study of a Caucasian population from the Netherlands also
reported no association of TNF
a
-308A with COPD (132). However, these
authors did find an association of COPD with the presence of the A allele of
another TNF
a
polymorphism (TNF
a
G489A). This association was only
found in patients who had no evidence of emphysema based on high resolu-
tion CT scans, consistent with the hypothesis that TNF
a
polymorphisms
would affect airway inflammation rather than proteolytic destruction of
the lung. In summary, the role of TNF
a
polymorphisms in COPD has
yet to be established, but this may be an another example of ethnic group
specific genetic risk factors.
IL-1 Complex:
The IL-1 family consists of two proinflammatory
cytokines, IL-1
a
and IL-1
b
, and a naturally occurring anti-inflammatory
agent, the IL-1 receptor antagonist (IL1RN). The two forms of IL-1 are
the products of different genes, but they are structurally related and bind
to the same receptor. IL-1
a
and IL-1
b
are synthesized by a variety of cell
types, but mainly monocytes and macrophages. IL1RN is a protein that
binds to the IL-1 receptor with the same affinity as IL-1, but does not pos-
sess agonist activity and therefore acts as a competitive inhibitor of IL-1
(133). The genes of the IL-1 complex are found in close proximity on the
long arm of human chromosome 2 (134), and each of the genes is poly-
morphic. The IL-1
b
gene (IL1B) has a single nucleotide polymorphism in
the promoter region (C-511T) (135), and the IL1RN gene has a polymorphic
