C. Vergara

Association between total immunoglobulin E and antibody responses to naturally acquired Ascaris lumbricoides infection and polymorphisms of immune system-related LIG4, TNFSF13B and IRS2 genes

The 13q33–34 region harbours a susceptibility locus to Ascaris lumbricoides, although the underlying genes are unknown. Immunoglobulin (Ig)E and IgG confer protective immunity and here we sought to investigate in an endemic population whether LIG4, TNFSF13B and IRS2 genes influence IgE and IgG levels against Ascaris and the ABA‐1 allergen as a putative resistance marker. Mite‐allergic asthmatic patients were analysed for potential relationships between Ascaris predisposition and allergy. One thousand and sixty‐four subjects from Cartagena, Colombia, were included. Single nucleotide polymorphisms (SNPs) were genotyped using TaqMan assays. Antibody levels were measured by enzyme‐linked immunosorbent assay. Linear and logistic regressions were used to model effects of genotypes on antibody levels. The GG genotype of LIG4 (rs1805388) was associated with higher IgE levels to Ascaris compared with other genotypes. TNFSF13B (rs10508198) was associated positively with IgG levels against Ascaris extract and IgE levels against ABA‐1. In asthmatics, IRS2 (rs2289046) was associated with high total IgE levels. Associations held up after correction by population stratification using a set of 52 ancestry markers, age, sex and disease status. There was no association with asthma or mite sensitization. In a tropical population, LIG4 and TNFSF13B polymorphisms are associated with specific IgE and IgG to Ascaris, supporting previous linkage studies implicating the 13q33 region. Our results suggest that genes protecting against parasite infections can be different to those predisposing to asthma and atopy.

A Six-SNP Haplotype of ADAM33 Is Associated with Asthma in a Population of Cartagena, Colombia

Background: A disintegrin and metalloprotein-33 (ADAM33) participates in the bronchial remodeling process in asthma, and genetic analyses pointed it out as a candidate gene in asthma. Methods: To analyze the association between ADAM33 and asthma and total and mite-specific IgE levels in a population of the Caribbean Coast of Colombia, we genotyped 6 single-nucleotide polymorphisms of ADAM33 in 429 asthmatics, 401 controls and 116 family trios using fluorogenic probes. Total and specific IgE against Blomia tropicalis and Dermatophagoides pteronyssinus were determined by ELISA. Case-control and family-based analyses were performed. Case-control association analyses were corrected by population stratification using a set of 52 ancestry-informative markers. Results: Eight common haplotypes were identified; among them, H4 (GCAGGG) was associated with asthma in the family group (Z score: –2.049, p = 0.04). We also found an association between the TT genotype of ST+7 and asthma in the case-control study (p = 0.05) that disappeared after correcting for multiple testing. In the family-based analysis, this genotype was a risk factor for asthma (p = 0.01), high total IgE (Z score: 2.546, p = 0.01) and high specific IgE against B. tropicalis (p = 0.02) and D. pteronyssinus (Z score: 2.414, p = 0.01). V4 was associated with specific IgE against B. tropicalis (p = 0.03); T2 with asthma (p = 0.03), high total IgE (p = 0.02) and IgE against D. pteronyssinus (p = 0.03) and T1 with high total IgE (p = 0.04). None of these associations was maintained after correction for multiple testing. Conclusions: Our findings suggest a relevant role of ADAM33 in thepathogenesis of asthma in this population.

Asthma Mortality in Colombia

Background Asthma mortality rates have increased in several industrialized countries during the past two decades. In Latin America, there have been reported only a few national studies of asthma mortality. Objective To determine asthma mortality rates in Colombia from 1979 to 1994. Methods Death certificates from the National Administrative Statistical Department of Colombia were collected and analyzed. Results For the entire population we found increasing rates of asthma mortality from 2.15 in 1979 to 3.3 in 1985 followed by a decrease to 1.6 in 1994. Overall, the trend has been to decrease, with a variation coefficient of 1.09% by year. Age-adjusted rates of death from asthma, based on the population distribution of 1973, showed the same decreasing trend. Deaths from asthma were more frequent in subjects older than 35 years as compared with those younger than 5 years of age or the age group ranging from 5 to 34 years. For the latter, rates of death increased from 0.32 in 1980 to 0.37 in 1988, and fell to 0.20 in 1991. From 1992 to 1994 rates for 5 to 34 years of age were higher than previously, increasing to 0.9 in 1992 and decreasing to 0.6 in 1994. There was no significant variation in death rates between men and women. Sixty-two percent of deaths from asthma occurred at home, 31% at hospitals, and 6.7% in other places. Most asthma deaths were in urban areas. Conclusions In contrast to that observed in industrialized countries, we found a decreasing trend in asthma mortality in Colombia. Rates of death from asthma, however, are still high in this country.

A NOS1 gene polymorphism associated with asthma and specific immunoglobulin E response to mite allergens in a Colombian population.

Background: Nitric oxide (NO) is involved in asthma pathogenesis and is synthesized by three isoforms of NO synthase, one of them encoded by NOS1 gene. The CA-repeat and the C5266T SNP in NOS1 exon 29 have been associated with asthma and IgE levels. We thought to test the association of asthma and asthma-related phenotypes with the exon 29 CA-repeat and the C5266T SNP in a Colombian population sample. Methods: The CA-repeat and the C5266T SNP were genotyped in 167 asthmatics and 166 controls using PCR-based fragment length polymorphism and TaqMan assay. We also determined total and mite-specific IgE against Blomia tropicalis and Dermatophagoides pteronyssinus. Results: Three new CA-repeat alleles, 14, 23 and 24 repeats were detected. Allele comprising 16 repeats was associated with asthma (OR: 1.90 (CI 1.22–2.97, pc = 0.028) and low total (pc = 0.02) and specific IgE to B. tropicalis (pc < 0.0001) and D. pteronyssinus (pc < 0.0001). We found no association of the C5266T SNP and asthma or IgE levels. Conclusion:NOS1 exon 29 CA-repeat may be a risk factor for asthma susceptibility and mite specific IgE response in a Colombian population.

Association of G-protein-coupled receptor 154 with asthma and total IgE in a population of the Caribbean coast of Colombia.

Background G protein‐coupled receptor 154 was described as an asthma susceptibility gene by positional cloning. It has been subsequently associated with asthma and other inflammatory diseases in several populations with different ethnic origin. Replication of associations adds reliability to these findings.

The C-509T promoter polymorphism of the transforming growth factor beta-1 gene is associated with levels of total and specific IgE in a Colombian population.

Background: The C-509T polymorphism of the transforming growth factor beta-1 (TGFB1) gene has been associated with asthma and asthma-related phenotypes, but its influence on total and specific IgE levels is controversial. Objective: To investigate the association between C-509T and asthma, as well as total IgE and specific IgE against Blomia tropicalis and Dermatophagoides pteronyssinus, in a Colombian population. Methods: The study population consisted of 417 asthmatics, 390 controls and 116 nuclear families. The C-509T polymorphism was genotyped using single-base extension minisequencing or Taq Man probes. IgE and TGFβ1 levels were measured by ELISA. Regression analysis and family-based association tests were performed in cases/controls and families. Associations were corrected by population structure using a panel of 52 ancestry informative markers in the case-control dataset. Results: There was no association between C-509T and asthma. In asthmatics, the CC genotype was associated with higher total IgE levels compared with the other genotypes [mean IgE: 2.81 ± 0.42 vs. 2.71 ± 0.45 log IU/ml; p = 0.016, corrected p value (pc) = 0.019]. When only atopic asthmatics were included, the significance remained (p = 0.02, pc = 0.03). In the family-based analyses, the C allele was associated with higher total IgE levels (p = 0.02) and the CC genotype with specific IgE to D. pteronyssinus (p = 0.01). Conclusions: C-509T is associated with total IgE levels and specific IgE to D. pteronyssinus in asthmatic patients. In contrast to other studies, we found the CC genotype to be associated with higher levels of total and specific IgE. Differences in the frequency of this allele among populations could alter its effects as a risk factor for asthma-associated phenotypes.