0
Clinical Investigations: ASTHMA |

Association of Asthma Severity and Bronchial Hyperresponsiveness With a Polymorphism in the Cytotoxic T-Lymphocyte Antigen-4 Gene*

Sang Yeub Lee, MD; Young Ho Lee, MD; Chol Shin, MD; Jae Jeong Shim, MD; Kyung Ho Kang, MD, FCCP; Se Hwa Yoo, MD; Kwang Ho In, MD
Author and Funding Information

*From the Division of Pulmonology (Drs. S. Y. Lee, Shin, Shim, Kang, Yoo, and In), and the Division of Rheumatology (Dr. Y. H. Lee), the Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea.

Correspondence to: Kwang Ho In, MD, Division of Pulmonology, Department of Internal Medicine, Korea University Anam Hospital 126-1, 5Ka, Anam-Dong, Sungbuk-Ku, Seoul, Korea, 136–075; e-mail: khin@ns.kumc.or.kr



Chest. 2002;122(1):171-176. doi:10.1378/chest.122.1.171
Text Size: A A A
Published online

Objectives: Cytotoxic T-lymphocyte antigen (CTLA)-4 is a homolog of CD28, which is expressed only on activated T cells. It binds to accessory molecule B7 and mediates T-cell-dependent immune response. Signaling through CTLA-4 may down-regulate type 1 T-helper cell proliferation; moreover, some studies suggest that CTLA-4 might also deliver a positive signal to type 2 T-helper cell activation. Disruption of this delicate balance of immune regulation may lead to autoimmune diseases or atopic diseases. To evaluate the possible role of CTLA-4 polymorphisms in bronchial asthma, we investigated the association between polymorphisms (exon 1 +49 A/G, promoter −318 C/T) and atopy, asthma severity, and bronchial hyperresponsiveness in bronchial asthma patients and a group of healthy control subjects.

Patients: Eighty-eight asthmatic patients and 88 healthy control subjects were studied.

Measurements and results: Asthma severity assessment, methacholine challenge, allergy skinprick test, and serum total IgE measurements were performed. The genotypes of the CTLA-4 promoter (−318 C/T) and exon 1 (+49 A/G) in all subjects were determined using the polymerase chain reaction and restriction fragment length polymorphism. The CTLA-4 promoter (−318 C/T) polymorphism was shown to be associated with asthma severity, but not with asthma, atopy, or bronchial hyperresponsiveness. A significant association was found between severe asthma and the T allele (p = 0.037). The CTLA-4 exon 1 (+49 A/G) polymorphism was shown to be associated with bronchial hyperresponsiveness, but not with asthma, atopy, or asthma severity. Asthmatic patients of the GG genotype had more hyperresponsive airways than those with the AG or AA genotype (p = 0.019).

Conclusions: The CTLA-4 promoter (−318 C/T) T allele may serve as a clinically useful marker of severe asthma. The CTLA-4 exon 1 (+49 A/G) polymorphism may have a disease-modifying effect in asthmatic airways.

Figures in this Article

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Figures

Tables

References

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543