Genome-Wide Linkage Analyses
The CSGA included Hispanic families, most of whom came from an area of Albuquerque (New Mexico) where 38% of Hispanics are of Mexican descent and 60% of Hispanics identify themselves as other Hispanic or Latino. The initial genome-wide linkage analysis of asthma in the CSGA included 48 Hispanics with asthma in 18 families. This analysis identified a modest evidence of linkage (p < 0.01) between two genomic regions (chromosomes 2q and 21q) and asthma among Hispanics. After the inclusion of 12 additional families, a repeat genome-wide analysis showed suggestive evidence of linkage (maximum LOD, 2.9) between chromosome 1p and asthma in Hispanics.
Among Hispanics in the CSGA, Mathias et al showed modest evidence of linkage (maximum LOD = 1.5) between two chromosomal regions (9q and 12p) and total serum IgE level. In addition, Blumen-thal et al showed suggestive evidence of linkage between chromosome 21q and atopy (maximum LOD, 2.2) in Hispanics.
Selected Candidate-Gene Association Studies
ADAM33: Among 112 Hispanics with asthma who participated in the CSGA and 126 control subjects, Howard et al found an association between SNPs in ADAM33 and asthma and allergen sensitization. In contrast, there was no association between six SNPs in ADAM33 and asthma or asthma-related phenotypes in a study of 583 nuclear families (265 Mexican families and 318 Puerto Rican families) of Hispanics with asthma in the Genetics of Asthma in Latino Americans study. Of note, this study recruited families living in different environments (Puerto Rican families from New York and Puerto Rico, and Mexican families from San Francisco and Mexico City). Among 47 nuclear families of Hispanic children with asthma, Raby et al found no significant association between any of 17 SNPs in the ADAM33 gene and asthma or asthma-related phenotypes after adjustment for multiple comparisons.
ADRB2: The ADRB2 gene is on chromosome 5q31-33, which is a region linked to asthma phenotypes. SNPs and/or haplotypes in the ADRB2 gene have been associated with the response to inhaled P2-agonists, asthma severity,” and other asthma-related phenotypes. Among Mexican adults with asthma (n = 303) and without asthma (n = 604) in Monterrey (Mexico), Santillan and colleagues found an inverse association between alleles (Glu27) and haplotypes (Gly16-Glu27) in the ADRB2 gene and asthma. Choudry et al tested for an association between seven SNPs in the ADRB2 gene and asthma-related phenotypes (ie, asthma severity, bronchodilator responsiveness, and total serum IgE level) in Puerto Rican (n = 393) and Mexican (n = 274) families of asthmatics in the Genetics of Asthma in Latino Americans Study. Among Puerto Rican families, two SNPs (A-654G and A 46G [Arg16Gly]) were associated with baseline FEV1 and bronchodilator responsiveness. Among Mexican families, only one SNP (G 79C [Glu27Gln]) was marginally associated with bron-chodilator responsiveness. Confirmatory analyses in the Puerto Rican probands (index cases) showed an association between the number of Arg16 alleles in the ADRB2 gene and bronchodilator responsiveness only among subjects with reduced lung function.
IL4 and IL4R Genes: Among 116 Hispanics with asthma in the CSGA and 130 control subjects, 2 of 11 SNPs in the IL4 gene were associated with total serum IgE level (p = 0.01 to 0.02), but no significant association was found between any of the 11 SNPs in the IL4 gene and asthma. Among 30 Hispanic families in the CSGA, there was no association between any of five SNPs in the IL4R gene and atopy, and only one SNP in the IL4R gene was weakly associated with asthma (p = 0.03).
IL13 Gene: IL-13 has been implicated in the regulation of IgE synthesis and the pathogenesis of asthma and a coding SNP ( 2044 or Arg130Gln) in exon 4 of the IL13 gene was associated with total serum IgE level among nonatopic whites. Celedon et al found no association between the Arg130Gln allele of IL13 and asthma or asthma-related phenotypes (total serum IgE level and allergen sensitization) in 83 nuclear families of children with asthma in Costa Rica.