Beta(2)-adrenergic receptor allele frequencies in the Quechua, a high altitude native population

The beta(2)-adrenergic receptor is: involved in the control of numerous phy siological processes and, as the primary catecholamine receptor in the lung s, is of particular importance in the regulation of pulmonary function. The re are several polymorphic loci in the beta(2)-adrenergic receptor gene tha t have alleles that alter receptor function, including two (A/G(46): G/C-79 ) that increase agonist sensitivity. As such a phenotype may increase vase and bronchial dilation, thereby facilitating air and blood flow through the lungs, we hypothesized that selection may have favoured these alleles in h igh altitude populations as part of an adaptive strategy to deal with the h ypoxic conditions characteristic of such environments. We tested this hypot hesis by determining the allele frequencies for these two polymorphisms, as well one additional missense mutation (C/T-491) and two silent mutations ( G/A(252) and C/A(523)) in 63 Quechua speaking natives from communities loca ted between 3200 and 4200 m on the Peruvian altiplano. These frequencies we re compared with those of two lowland populations, one native American (Na- Dene from the west coast of Canada) and one Caucasian of Western European d escent. The Quechua manifest many of the pulmonary characteristics of high altitude populations and differences in allele frequencies between the Quec hua and lowlanders could be indicative of a selective advantage conferred b y certain genotypes in high altitude environments. Allele frequencies varie d between populations at some loci and patterns of linkage disequilibrium d iffered between the old-world and new-world samples; however, as these popu lations are not closely related, significant variation would be expected du e to stochastic effects: alone. Neither of the alleles associated with incr eased receptor sensitivity (A(46), G(79)) was significantly over-represente d in the Quechua compared with either lowland group. The Quechua were monom orphic for the C allele at base 79, This variant has been associated with b ody mass index; howes er no clearly defined metabolic phenotype has been es tablished. In addition, we sequenced the coding region of the gene in three unrelated Quechua to determine if there were any other polymorphisms commo n in this population. None were detected.