Biomedical Engineering Reference
In-Depth Information
their other chromosome (166). In addition, all the studies described earlier
were based on small numbers of subjects and only three (161-163) compared
cases to controls. The other studies compared frequencies in the cases with
published allele frequencies, and therefore the results of these studies are far
from definitive.
IV. CONCLUSIONS
Although there is clear evidence of a genetic contribution to the pathogen-
esis of COPD, few specific genes have been implicated to date. Most studies
have been case-control candidate gene studies and were often too small in
size to be powerful enough to detect genes of modest effect. In addition,
the reported studies have been mostly limited to known biologically plausi-
ble candidates. In earlier onset diseases, such as asthma, large-scale family
studies have provided clues as to the location of susceptibility genes using
the technique of genome-wide screening. This technique can identify
susceptibility genes irrespective of whether the biological function is known.
In the future, more information about the role of genetic risk factors in
the development of COPD may be provided by large-scale family studies,
genome-wide association studies, and investigation of an increased number
of possible candidate genes identified by the Human Genome Project.
REFERENCES
1. Larson RK, Barman ML. The familial occurrence of chronic obstructive
pulmonary disease. Ann Intern Med 1965; 63:1001-1008.
2. Tager IB, Rosner B, Tishler PV, Speizer FE, Kass EH. Household aggregation
of pulmonary function and chronic bronchitis. Am Rev Respir Dis 1976;
114:485-492.
3. Lebowitz MD, Knudson RJ, Burrows B. Family aggregation of pulmonary
function measurements. Am Rev Respir Dis 1984; 129:8-11.
4. Speizer FE, Rosner B, Tager I. Familial aggregation of chronic respiratory
disease: use of National Health Interview Survey data for specific hypothesis
testing. Int J Epidemiol 1976; 5:167-172.
5. Larson RK, Barman ML, Kueppers F, Fudenberg HH. Genetic and environ-
mental determinants of chronic obstructive pulmonary disease. Ann Intern
Med 1970; 72:627-632.
6. Cohen BH, Diamond EL, Graves CG, Kreiss P, Levy DA, Menkes HA,
Permutt S, Quaskey S, Tockman MS. A common familial component in lung
cancer and chronic obstructive pulmonary disease. Lancet 1977; 2:523-526.
7. Silverman EK, Chapman HA, Drazen JM, Weiss ST, Rosner B, Campbell EJ,
O'Donnell WJ, Reilly JJ, Ginns L, Mentzer S, Wain J, Speizer FE. Genetic
epidemiology of severe, early-onset chronic obstructive pulmonary disease.
Risk to relatives for airflow obstruction and chronic bronchitis. Am J Respir
Criti Care Med 1998; 157:1770-1778.
