The CC chemokine regulated upon activation, normal T-cell exsome 17q (5,6), where the gene encoding RANTES is located, the RANTES promoter region (7, 9), whereas another ge-83 middle-onset patients with asthma (onset at 20 to 40 years of netic study found a significant association of the Ϫ403A allele age), and 98 early-onset patients with asthma (onset at less than with atopy and asthma in adults (10). 20 years of age). The Ϫ28G allele was significantly associated with late-onset asthma (odds ratio ϭ 2.033; 95% confidence interval,The age at onset of asthma covers a wide range. Almost in the pathophysiology of asthma that develops in later life Our findings suggest that, among Japanese, the Ϫ28G allele of (12). Furthermore, the age at onset of asthma correlates the RANTES promoter region confers susceptibility to late-onset with reactivity of basophils; early-onset asthma is significantly asthma.associated with greater levels of anti-immunoglobulin E (IgE)-induced histamine release from basophils (13). In a Keywords: late-onset asthma; RANTES; single nucleotide polymorphism previous study, we found that the age at onset of asthma (SNP)

A number of chemokines are produced by alveolar cells in the course of inflammatory reactions of sarcoidosis. C-C chemokine receptor 2 (CCR2) is a prominent receptor for the monocyte chemoattractant protein (MCP) group of C-C chemokines. A transition causing a valine to isoleucine substitution in transmembrane domain I of the CCR2 gene (CCR2-64I) that has a protective effect against the progression of human immunodeficiency virus-1 (HIV-1) disease has been described. To elucidate the role of this CCR2 polymorphism in sarcoidosis, we investigated the distribution of the CCR2-64I in 100 subjects with sarcoidosis (40.2 +/- 18.6 yr [mean +/- SD], 37:63 [male:female]) and 122 healthy control subjects (44.4 +/- 14.1 yr, 75:47). The distribution of the CCR2-64I allele was significantly different between subjects with sarcoidosis and healthy control subjects (p < 0.001). The presence of the CCR2-64I allele conferred a lower risk for the development of sarcoidosis (adjusted odds ratio = 0.369, 95% CI = 0.203 to 0.673). Our study suggests that this polymorphism may play a role in the pathogenesis of sarcoidosis, and further studies are needed to define the role of CCR2-64I.

Genetic factors are important in defining total serum IgE levels. Linkage analyses have localized a gene or genes that influence atopic phenotype at chromosome 11q13. Variants of the FCER1B gene have been identified, which are associated with an increased risk of developing atopy and bronchial asthma. Given uncertain functional consequences and low frequencies of these coding variants of FCER1B , we screened for new mutations using 24 subjects with atopic asthma. A common Ϫ 109C/T polymorphism at the promoter region of FCER1B was identified, although no variant was found in the entire coding region. We genotyped this promoter polymorphism in 226 healthy control subjects and 226 asthmatic subjects using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Allele frequencies were 0.697 for Ϫ 109T and 0.303 for Ϫ 109C in 226 healthy control subjects. No significant difference in the distribution of Ϫ 109C/T polymorphism was found between asthmatic subjects and healthy control subjects. A homozygosity for the Ϫ 109T allele, however, was associated with increased total serum IgE levels in 226 subjects with asthma (p ϭ 0.0015). The strongest evidence for an association between total serum IgE levels and Ϫ 109C/T polymorphism (p ϭ 0.0004) was obtained when age at onset of asthma was incorporated into the analysis. Our findings may represent genetic heterogeneity and complex interactions between genetic and environmental components involved in the regulation of total IgE levels, providing evidence that the Ϫ 109C/T polymorphism of the FCER1B promoter region is one of the genetic factors identified thus far, which affects total serum IgE levels in a Japanese population. Hizawa N, Yamaguchi E, Jinushi E, Kawakami Y. A common FCER1B gene promoter polymorphism influences total serum IgE levels in a Japanese population. Total serum IgE levels are a quantitative trait associated with atopic diseases including bronchial asthma, allergic rhinitis, and atopic dermatitis. Immunoglobulin E-dependent activation of mast cells and basophils through the high-affinity IgE receptor (Fc ε RI) is involved in the pathogenesis of allergeninduced immune responses in atopic diseases. Several studies have reported linkage or association between the measures of atopy and chromosome 11q13 (1-3). The gene encoding the ␤ subunit of the high-affinity IgE receptor in this chromosomal region is considered to be the most likely candidate for these findings (4). Recently, animal models have provided unequivocal genetic evidence that Fc ε RI-␤ functions as an amplifier of immune responses, especially those induced by mast cells and basophils (5).Three coding variants, I181L/V183L, I181L, and E237G in the FCER1B gene have previously been described. An isoleucine to leucine substitution at position 181 (I181L) of Fc ε RI-␤ is associated with atopy through maternal descent in a British population (6). In addition, a glutamic acid-to-glycine substitution (E237G) occurs in approximately 5% of Australian and British populati...

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