Method for predicting risk of developing chronic pulmonary...

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid

Reexamination Certificate

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C435S091100, C536S023100

Reexamination Certificate

active

06436645

ABSTRACT:

CROSS-REFERENCE TO RELATED APPLICATIONS
This application is based upon and claims the benefit of priority from the prior Japanese Patent Application No. 11-334248, filed Nov. 25, 1999, the entire contents of which are incorporated herein by reference.
BACKGROUND OF THE INVENTION
The present invention relates to a method for predicting the risk of developing chronic pulmonary emphysema.
Chronic pulmonary emphysema (hereinafter referred to as “CPE”) has increased due to the changing circumstances in the Japanese society, habitual smoking, and aging. When a person suffers from chronic dyspnea, a daily life is limited. Furthermore, respiratory tract infection leads to breathing difficulties (respiratory insufficiency). Therefore, it is an urgent business to clarify pathogenesis and prophylaxis of CPE.
Smoking is considered as a major risk factor for causing CPE. However, the risk of smokers developing CPE is only 10-15%. Therefore, environmental and genetic factors other than smoking may be responsible for causing CPE.
A protease/anti-protease imbalance theory has been proposed as an etiological factor for CPE. For example, &agr;1-antitrypsin deficiency has been reported to cause CPE. Recently, a theory of alveoli destruction due to oxidant/anti-oxidant imbalance has been also proposed as a cause.
However, even though there are several percentages of patients suffering from the &agr;1-antitrypsin deficiency in Western countries, only few cases have been reported in Japan. Accordingly, it may not be safe to determine that the &agr;1-antitrypsin deficiency is a major etiological cause of CPE, at least in Japan.
BRIEF SUMMARY OF THE INVENTION
The present invention relates to a method for predicting the possible risk of a subject developing CPE by determining how many times GT is repeated in a GT repeat sequence which is located upstream of a gene encoding hemeoxigenase-1 conceivable as an etiological factor for CPE.
More specifically, the method for predicting the possible risk of a subject developing CPE, comprises the steps of:
(a) preparing a test sample taken from a subject containing at least one GT repeat sequence located upstream of a hemeoxygenase-1 gene;
(b) determining the number of times GT is repeated in the GT repeat sequence; and
(c) determining that the risk of a subject developing CPE is high if the number of times GT is repeated not less than 30.
The invention also relates to an apparatus for predicting the possible risk of a subject developing CPE by determining how many times GT is repeated in a GT repeat sequence which is located upstream of a gene encoding hemeoxigenase-1 conceivable as an etiological factor for CPE.
Additional objects and advantages of the invention will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. The objects and advantages of the invention may be realized and obtained by means of the instrumentalities and combinations particularly pointed out hereinafter.


REFERENCES:
Yamada et al. “Microsatellie polymorphism in the heme oxygenase-1 gene promoter is associated with susceptibility to emphysema”. Am. J. Hum. Genet. vol. 66, pp. 187-195, Jan. 2000.*
Shigeki Shibahara, et al., “Structural Organization of the Human Heme Oxygenase Gene and The Function of Its Promoter”, Eur. J. Biochem 179, pp. 557-563 (1989).
Shoji Okinaga, et al., “Regulation of Human Heme Oxygenase-1 Gene Expression Under Thermal Stress”, Blood, vol. 87, No. 12, Jun. 15, 1996, pp. 5074-5084.
Teiko Kimpara, et al., “Microsatellite Polymorphism in the Human Heme Oxygenase-1 Gene Promoter and Its Application in Association Studies With Alzheimer and Parkinson Disease”, Hum Genet, 1997, 100: pp. 145-147.

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