G protein beta 3 gene

Recent studies have shown that a polymorphism (C825T) in the gene encoding the G protein beta 3 subunit (GNB3) is associated with hypertension and obe sity. We characterized the entire GNB3 gene, which spans 7.5 kb and is comp osed of 11 introns and 10 introns. Its promoter lacks a TATA box but harbor s GC-rich regions. The functional activity of the GNB3 promoter was verifie d with reporter gene assays that also demonstrated its inducibility by phor bol esters. A novel polymorphism in the promoter region A(-350)G occurred w ith frequencies (G allele) of 76%, 97%, and 61% in Africans, Chinese, and G ermans, respectively. Reporter gene constructs with either the A or the G a llele did not differ with regard to inducement of the reporter protein. A s ilent nucleotide exchange in the coding region (A657T) occurred with T alle le frequencies ranging from 0.5% to 2.4%. Another polymorphism (G814A) resu lts in the replacement of glycine by serine at position 272. In Germans, th e A allele occurred at a frequency of 10%. Finally, a C1429T polymorphism i n the 3' untranslated region of GNB3 was identified that occurred at T alle le frequencies of 38%, 17%, and 30% in Africans, Chinese, and Germans, resp ectively. Haplotype prediction indicated in Germans an almost complete asso ciation of GNB3 825T with 1429T, and vice versa. An analysis of these polym orphic loci in nonhuman primates revealed that the ancestral GNB3 gene harb ored the (-350)G, 825C, and 1429C alleles. This is the first complete chara cterization of the human GNB3 gene and its promoter region, which will enab le refined epidemiological and biochemical investigations of GNB3 in hypert ension and obesity.