title: Hypertension-susceptibility gene prevalence in the Pacific Islands and associations with hypertension in Melanesia.
abstract: Human essential hypertension is partly caused by genetic factors. Angiotensinogen (AGT), G-protein β3-subunit (GNB3) and cytochrome P450 3A5 (CYP3A5) are candidate hypertension susceptibility genes and risk alleles at these loci have been thought to arise owing to human adaptation to climatic changes following the migration out-of-Africa. This study aimed to reveal the frequencies of hypertension-susceptibility genotypes in Pacific Island populations and associations of these single-nucleotide polymorphisms (SNPs) to hypertension. Genotyping was conducted for 804 individuals from Melanesian, Micronesian and Polynesian populations at SNPs in the genes encoding AGT (rs699, rs5049 and rs5051), GNB3 (rs5443) and CYP3A5*1/*3 (rs776746). Associations between these SNPs and hypertension were tested for 383 Melanesian Solomon Islanders. We found that the A/A genotype at rs5049 was a risk factor for hypertension (P=0.025) in the Melanesian Solomon Islanders; three SNPs for AGT were in linkage disequilibrium. The ancestral alleles of rs699, rs5051 and rs776746, and the derived allele of rs5443 were as frequent in the populations surveyed here as in other equatorial populations. Although other polymorphisms associated with hypertension and additional populations remain to be studied, these findings suggest that the Pacific Islanders' susceptibility to hypertension arose because of human migration and adaptation.
authors: Graduate School of Asian and African Area Studies, Kyoto University, Kyoto, Japan. takuro.f@gmail.com
authors: Takuro
authors: T
authors: Furusawa
authors: Izumi
authors: I
authors: Naka
authors: Taro
authors: T
authors: Yamauchi
authors: Kazumi
authors: K
authors: Natsuhara
authors: Ricky
authors: R
authors: Eddie
authors: Ryosuke
authors: R
authors: Kimura
authors: Minato
authors: M
authors: Nakazawa
authors: Takafumi
authors: T
authors: Ishida
authors: Tsukasa
authors: T
authors: Inaoka
authors: Yasuhiro
authors: Y
authors: Matsumura
authors: Yuji
authors: Y
authors: Ataka
authors: Ryutaro
authors: R
authors: Ohtsuka
authors: Jun
authors: J
authors: Ohashi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000808:Angiotensinogen / Q000235:genetics*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D063426:Human Migration; D006801:Humans; D006973:Hypertension / Q000453:epidemiology* / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008542:Melanesia / Q000453:epidemiology; D008875:Middle Aged; D010139:Pacific Islands / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D012307:Risk Factors; D055815:Young Adult
chemical_list: C534931:AGT protein, human; C454420:G-protein beta3 subunit; D000808:Angiotensinogen; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D020962:Heterotrimeric GTP-Binding Proteins