Polymorphism of the immune-braking gene CTLA-4 (+49) involved in gender discrepancy of serum total IgE levels and allergic diseases


Address for reprints: Kuender D. Yang, MD at office of vice superintendents, Chang Gung Memorial Hospital at Kaohsiung, 123, Ta-Pei Rd, Niau-Sung Hsiang, Kaohsiung 833, Taiwan. E-mail: yangkd@adm.cgmh.org.tw


Background A variety of genes are related to allergic disorders in different ethnic populations. The genetic basis for the gender discrepancy of allergic diseases remains to be determined.

Objective This study was conducted to investigate whether IL-4 promoter (−590 C/T) and cytotoxic T lymphocyte antigen 4 (CTLA-4) (+49 A/G) polymorphisms were correlated with a gender discrepancy of total IgE levels and allergic diseases in a Chinese population.

Methods A total of 1333 participants aged 19–49 years were enrolled in this study. Allergic diseases were recognized by the presence of asthma, rhinitis or atopic dermatitis in conjunction with detectable specific IgE in the blood. Polymorphisms of IL-4 promoter (−590) and CTLA-4 (+49) were determined by restriction fragment length polymorphism.

Results Males or females with allergic diseases had higher total IgE levels than those without (P=0.000). Females with the A/A genotype in the CTLA-4 (+49) position had significantly higher total IgE levels than those with A/G, and those with the G/G genotype had the lowest IgE levels (154.9 vs. 107.1 vs. 79.8 KU/L; mean log values: 1.79 vs. 1.65 vs. 1.54, P< 0.001). However, males with different genotypes in the CTLA-4 (+49) position exhibited no difference in the total IgE levels. Females with allergic rhinitis had a significantly higher frequency of the A/A genotype in the CTLA-4 (+49) polymorphism than those without atopic diseases (P=0.016). In contrast, males with and without allergic disorders exhibited no significant difference in the CTLA-4 (+49) polymorphisms (P>0.05). The IL-4 promoter (–590) polymorphisms, however, had no correlation with the total IgE levels or allergic diseases in either females or males.

Conclusion In females only, the CTLA-4 (+49), but not the IL-4 promoter (−590), polymorphism was significantly associated with elevation of total IgE levels and allergic rhinitis. Here, we have, for the first time, demonstrated a gender-linked genetic relationship with allergic disease.