Genetic variants in the mannose receptor gene (MRC1) are associated with asthma in two independent populations

Abstract

Mannose receptor is a member of the C-type lectin receptor family involved in pathogen molecular pattern recognition and thought to be critical in shaping host immune responses and maintaining homeostasis. The aim of this study was to investigate potential associations of genetic variants in the MRC1 gene with asthma in two independent populations. Seven single-nucleotide polymorphisms (SNPs; rs2477637, rs2253120, rs2477631, rs2477664, rs692527, rs1926736, and rs691005) in the MRC1 gene locus were genotyped and evaluated regarding association with asthma in 870 unrelated Japanese subjects (446 asthmatics, 424 controls). The same markers were validated in 176 unrelated African-American subjects (86 asthmatics, 90 controls). Suggestive evidence of association between five SNPs (rs2477637, rs2253120, rs2477664, rs692527, and rs1926736) and asthma was observed in the analysis of the Japanese population independent of sex, age, smoking status, and atopic status. SNPs rs692527 and rs691005 showed significant association with asthma in the African-American population. Haplotypes containing two linked SNPs (rs692527 and rs1926736) were significantly associated with asthma in both Japanese and African-American populations. Our results suggest that sequence variations in the MRC1 gene are associated with the development of asthma in two independent and ethnically diverse populations.

The Mannose Receptor Mediates the Uptake of Diverse Native Allergens by Dendritic Cells and Determines Allergen-Induced T Cell Polarization through Modulation of IDO Activity

“…MR expression has been shown to be higher on DCs from atopic donors (14), and as such, it is reasonable to assume that the allergen-induced Th2 cell polarization seen in atopic donors could, at least in part, be due to a more efficient uptake of allergen through MR. Within this context, it is interesting to note that mapping analyses in mouse (13) and human (12) have identified Mrc1 (MR C-type 1) as a positional candidate gene for allergen-induced hyperresponsiveness, thus showing a clear association between MR and asthma. In a recent study, Hilmenyuk et al (32) have shown the impact of glycation, and in particular the presence of advance glycation end products (AGEs), on the immunogenicity and allergenicity of the model allergen OVA.…”

“…These DCs were unable to polarize Th1 effector cells and did not secrete the chemokines CXCL10 and CCL19 but produced large amounts of CCL22 and CCL17, thus favoring the amplification of Th2 circuits. These observations, together with others showing 1) that the MR gene is a candidate for allergen-induced airway hyperresponsiveness (12,13), 2) higher MR expression in atopic patients compared with that in healthy donors (14), and 3) MR contribution to the inhibitory effect of mannose-capped lipoarabinomannans on IL-12 production by DCs in response to LPS (15), suggest a putative role for MR in Th2 polarization. Interestingly, a recent study (14), using blocking carbohydrates, suggested that MR is responsible for 40-50% of the uptake of the major house dust mite allergen Der p 1 by human monocyte-derived DCs (Mo-DCs).…”

Polymorphisms in the sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8) gene are associated with susceptibility to asthma

“…The association with reduced risk of asthma was replicated for rs10409962 (OR, 0.73; 95% CI, 0.54-0.98; P¼0.032) but not for SNP rs36498 (OR, 1.04; 95% CI, 0.86-1.27; P¼0.67) and rs3829659 (OR, 0.86; 95% CI, 0.71-0.98; P¼0.088) (data not shown). As there Siglec-8 variations and asthma P-S Gao et al were significant differences in male/female, age distribution, atopy, and smoking status between the Japanese cases and controls (Po0.001 for all comparisons), 24 further analysis was performed by adjusting for age, sex, smoking, and atopic status, and we found that the association for SNP rs10409962 still remained significant (OR, 0.69; 95% CI, 0.50-0.94; P¼0.019; Table 2). None of the Siglec-8 SNPs were associated with tIgE in the Japanese population (data not shown).…”

“…Statistical analysis of the Japanese population used logistic regression analysis to estimate the odds ratio (OR) for asthma using an additive model adjusted and un-adjusted for gender, age, and smoking status using SYSTAT (version 10.2; Systat Inc., Chicago, IL, USA). 24 Statistical power for the case-control study was estimated using QUANTO (version 1.2)125. 32 …”

“…A total of 468 subjects with asthma (male, 47.0%, aged 45.9±16.8 years) and 457 healthy control subjects (male, 64.6%, aged 38.8±13.6 years) were recruited from the pulmonary clinic at the First Department of Medicine, Hokkaido University Hospital, as described previously. 24 The criteria for asthma in the Japanese population are presented in the Online Supplementary Information, and detailed clinical characteristics of these subjects are presented in Table 1.…”