RESUMO
The human beta-2 adrenergic receptor (beta2AR) is responsible for the binding of endogenous catecholamines and their exogenously administered agonists and antagonists. Three functional polymorphisms in codons 16, 27 and 164 have been described which have clinical importance for several diseases, including asthma, hypertension, heart failure, cystic fibrosis and obesity, as well as response to beta-agonist therapy. These were evaluated in 726 individuals from 8 distinct ethnic populations (Chinese, Filipino, Southwest Asian, Saudi, Ghanaian, Kenyan, Sudanese, and European from Scotland). The results show that most haplotypes are shared among all populations, yet there are marked differences in their frequency distributions geographically. The genetic distance tree is different from standard human population distance trees, implying a different mode of evolution for this locus than that for human population gene-flow history. The multilocus frequency differences between the observed clusters of populations correspond to historical haplotype groupings that have been found to be functionally different with respect to multiple medically related phenotypes. Further studies are needed to see if functional relationships are the same across populations.
Assuntos
Haplótipos/genética , Receptores Adrenérgicos beta 2/genética , Alelos , Povo Asiático/genética , População Negra/genética , Frequência do Gene , Genótipo , Humanos , Filogenia , Polimorfismo de Nucleotídeo Único , População Branca/genéticaAssuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Genes MDR , Metiltransferases/genética , Farmacogenética/métodos , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Nucleotídeo Único , Trifosfato de Adenosina/análise , Alelos , Substituição de Aminoácidos , Códon/genética , Difosfatos/análise , Eletroforese em Gel de Ágar , Genótipo , Humanos , Polimorfismo de Fragmento de RestriçãoRESUMO
HER-2, a protooncogene located on chromosome 17q21, encodes a transmembrane glycoprotein (p185) with tyrosine kinase activity. Alterations of the HER-2 gene have been implicated in the carcinogenesis and prognosis of breast cancer and other solid tumors. It is also a cancer-therapeutic target for antibody-based therapy against the HER-2 protein. A single-nucleotide polymorphism (SNP) at codon 655, resulting in a G-to-A transition (Ile655Val) in the transmembrane domain-coding region of this gene has been associated with an increased risk of breast cancer, particularly among younger women. To understand the importance of this finding throughout the world, we evaluated this polymorphism in Ghanaian, Kenyan, Sudanese, Caucasian, African-American, Saudi, and Filipino subjects using a polymerase chain reaction-restriction fragment length polymorphism assay. The frequency of the Val allele, which is associated with increased breast cancer risk, was highly variable between populations (0%-24%). Continental African populations had a lower frequency of the Val allele than did Saudi, Chinese, Filipino, Caucasian, and African-American subjects. The data suggest that this SNP has variable frequency in different ethnic groups. The findings in this study correspond with the lower incidence and lower risk of breast cancer in African women compared with Caucasian and African-American women.