Variability in TRBV haplotype frequency and composition in Caucasian, African American, Western African and Chinese populations.

The polymorphic T-cell receptor Vbeta (TRBV) genes encode much of the variable region of the T-cell receptor beta chain. Analysis of allele frequencies of three closely linked polymorphic TRBV genes, TRBV7-3, TRBV9 and TRBV6-4, was undertaken in several populations. The frequencies of these alleles are not significantly different in populations of Caucasians, African Americans and Western Africans. However, Chinese population is extremely homogenous at all three loci. The current study identifies the existence of haplotypic relationships between alleles of these genes in the Caucasian population. The ORF allele TRBV7-3*A3 is found exclusively on chromosomes bearing TRBV9*A2 and TRBV6-4*A2 in this cohort. In contrast, TRBV7-3*A1 and the null allele TRBV7-3*A2 are associated only with TRBV9*A1 and TRBV6-4*A1. This pattern of linkage disequilibrium (LD) is altered in the African American and Western African populations. In these cohorts, there is a marked reduction in LD between alleles of TRBV7-3 and TRBV9. This study is consistent with previous population genetic studies wherein African-derived samples have a greater level of genetic diversity compared to Caucasians. These data also demonstrate that patterns of LD are not consistent across the entire TRBV locus.

Analysis of the Ser786Pro interleukin-4 receptor alpha allelic variant in allergic and nonallergic asthma and its functional consequences.

Asthma and other atopic disorders affect a large percentage of the population. While many factors contribute to the phenotype of asthma, there is a strong genetic predisposition. IL-4 is a central mediator of allergic inflammation. Along with IL-13, it is the major cytokine responsible for the induction of IgE synthesis. Furthermore, IL-4 acts on Th0 cells and promotes their differentiation into Th2 cells resulting in the production of more IL-4 and IL-13, thereby propagating the allergic cascade. Both IL-4 and IL-13 utilize IL-4Ralpha as a component of their cognate receptor complexes. Eight polymorphisms of the IL-4Ralpha gene resulting in amino acid changes in the coding sequence have been described, and several have been associated with asthma. The central objective of this study was to elucidate the role of the Ser786Pro polymorphism in asthma and its impact on IL-4R function. One-hundred ninety-six individuals with asthma and 53 controls were genotyped for Pro786. Pro786 occurred infrequently in the general population with an allele frequency of 1.8% and, thus, is unlikely to play a major role in atopy or asthma. The Pro786 allele frequency was 1.5% in the asthma group and 2.8% in the control group. The asthma group was subdivided into allergic and nonallergic asthma, and the Pro786 allele frequencies were 1.7 and 1.0%, respectively. The data suggested linkage disequilibrium between Ser786Pro and the Gln576Arg allele, which is associated with atopy. In order to study the impact of the polymorphism on receptor signaling function, we transfected a mouse B lymphoma cell line with the wild-type and Pro786 variants of human IL-4Ralpha. The Ser786Pro polymorphism in isolation did not affect IL-4R function.

A novel polymorphism in the pseudogene TCRBV5S5 combines with TCRBV6S1 to define three haplotypes.

In the current study, we report a G to A single nucleotide polymorphism at base pair 396 of the TCRBV5S5P gene. This polymorphism has a frequency of 0.20 in a cohort of Caucasian controls. In addition, we provide evidence for linkage disequilibrium between TCRBV5S5P and the TCRBV6S1 gene.