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.
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References
WHO/ISH. World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension. J. Hypertens. 21, 1983–1992 (2003).
Eason, R. J., Pada, J., Wallace, R., Henry, A. & Thornton, R. Changing patterns of hypertension, diabetes, obesity and diet among Melanesians and Micronesians in the Solomon Islands. Med. J. Aust. 146, 465–469 (1987).
Natsuhara, K., Inaoka, T., Umezaki, M., Yamauchi, T., Hongo, T., Nagano, M. et al. Cardiovascular risk factors of migrants in Port Moresby from the highlands and island villages, Papua New Guinea. Am. J. Hum. Biol. 12, 655–664 (2000).
Marteau, J. B., Zaiou, M., Siest, G. & Visvikis-Siest, S. Genetic determinants of blood pressure regulation. J. Hypertens. 23, 2127–2143 (2005).
Langaee, T., Gong, Y., Yarandi, H., Katz, D., Cooper-DeHoff, R., Pepine, C. et al. Association of CYP3A5 polymorphisms with hypertension and antihypertensive response to verapamil. Clin. Pharmacol. Ther. 81, 386–391 (2007).
Watson, R. E., Karnchanasorn, R. & Gossain, V. V. Hypertension in Asian/Pacific Island Americans. J. Clin. Hypertens. 11, 148–152 (2009).
Young, J. H. Evolution of blood pressure regulation in humans. Curr. Hypertens. Rep. 9, 13–18 (2007).
Young, J. H., Chang, Y. P. C., Kim, J. D. O., Chretien, J. P., Klag, M. J., Levine, M. A. et al. Differential susceptibility to hypertension is due to selection during the out-of-Africa expansion. PLoS Genet. 1, e82 (2005).
Nakajima, T., Wooding, S., Sakagami, T., Emi, M., Tokunaga, K., Tamiya, G. et al. Natural selection and population history in the human angiotensinogen gene (AGT): 736 complete AGT sequences in chromosomes from around the world. Am. J. Hum. Genet. 74, 898–916 (2004).
Thompson, E., Kuttab-Boulos, H., Witonsky, D., Yang, L., Roe, B. & Di Rienzo, A. CYP3A variation and the evolution of salt-sensitivity variants. Am. J. Hum. Genet. 75, 1059–1069 (2004).
Neel, J. V. Diabetes mellitus: a ‘thrifty’ genotype rendered detrimental by ‘progress’? Am. J. Hum. Genet. 14, 353–362 (1962).
Diamond, J. M. Express train to Polynesia. Nature 336, 307–308 (1988).
Friedlaender, J. S., Friedlaender, F. R., Reed, F. A., Kidd, K. K., Kidd, J. R., Chambers, G. K. et al. The genetic structure of Pacific Islanders. PLoS Genet. 4, e19 (2008).
Kimura, R., Ohashi, J., Matsumura, Y., Nakazawa, M., Inaoka, T., Ohtsuka, R. et al. Gene flow and natural selection in oceanic human populations inferred from genome-wide SNP typing. Mol. Biol. Evol. 25, 1750–1761 (2008).
Oppenheimer, S. J. & Richards, M. Polynesian origins. Slow boat to Melanesia? Nature 410, 166–167 (2001).
Furusawa, T., Naka, I., Yamauchi, T., Natsuhara, K., Kimura, R., Nakazawa, M. et al. The Q223R polymorphism in LEPR is associated with obesity in Pacific Islanders. Hum. Genet. 127, 287–294 (2010).
Furusawa, T., Naka, I., Yamauchi, T., Natsuhara, K., Kimura, R., Nakazawa, M. et al. The serum leptin level and body mass index in Melanesian and Micronesian Solomon Islanders: focus on genetic factors and urbanization. Am. J. Hum. Biol. 23, 435–444 (2011).
Furusawa, T., Furusawa, H., Eddie, R., Tuni, M., Pitakaka, F. & Aswani, S. Communicable and non-communicable diseases in the Solomon Islands villages during recovery from a massive earthquake in April 2007. N. Z. Med. J. 124, 17–28 (2011).
Page, L., Damon, A. & Moellering, R. C. Antecedents of cardiovascular disease in six Solomon Islands societies. Circulation 49, 1132–1146 (1974).
Weiner, J. S. & Lourie, J. A. Practical Human Biology (Academic Press, London, 1981).
Aswani, S. Common property models of sea tenure: a case study from the Roviana and Vonavona Lagoons, New Georgia, Solomon Islands. Hum. Ecol. 27, 417–453 (1999).
Jeunemaitre, X., Soubrier, F., Kotelevtsev, Y. V., Lifton, R. P., Williams, C. S., Charru, A. et al. Molecular basis of human hypertension: role of angiotensinogen. Cell 71, 169–180 (1992).
Hata, A., Namikawa, C., Sasaki, M., Sato, K., Nakamura, T., Tamura, K. et al. Angiotensinogen as a risk factor for essential hypertension in Japan. J. Clin. Invest. 93, 1285–1287 (1994).
Kato, N., Sugiyama, T., Morita, H., Kurihara, H., Yamori, Y. & Yazaki, Y. Angiotensinogen gene and essential hypertension in the Japanese: extensive association study and meta-analysis on six reported studies. J. Hypertens. 17, 757–763 (1999).
Caulfield, M., Lavender, P., Farrall, M., Munroe, P., Lawson, M., Turner, P. et al. Linkage of the angiotensinogen gene to essential hypertension. N. Engl. J. Med. 330, 1629–1633 (1994).
Caulfield, M., Lavender, P., Newell-Price, J., Farrall, M., Kamdar, S., Daniel, H. et al. Linkage of the angiotensinogen gene locus to human essential hypertension in African Caribbeans. J. Clin. Invest. 96, 687–692 (1995).
Ghazali, D. M., Rehman, A. & Rahman, A. R. A. Candidate gene polymorphisms and their association with hypertension in Malays. Clin. Chim. Acta. 388, 46–50 (2008).
Inoue, I., Nakajima, T., Williams, C. S., Quackenbush, J., Puryear, R., Powers, M. et al. A nucleotide substitution in the promoter of human angiotensinogen is associated with essential hypertension and affects basal transcription in vitro. J. Clin. Invest. 99, 1786–1797 (1997).
Wu, D. M., Shen, M. H. & Chu, N. F. Relationship between plasma leptin levels and lipid profiles among school children in Taiwan: The Taipei Children Heart Study. Eur. J. Epidemiol. 17, 911–916 (2001).
Wu, S. J., Chiang, F. T., Jiang, J. R., Hsu, K. L., Chern, T. H. & Tseng, Y. Z. The G-217A variant of the angiotensinogen gene affects basal transcription and is associated with hypertension in a Taiwanese population. J. Hypertens. 21, 2061–2067 (2003).
Pereira, T. V., Nunes, A. C. F., Rudnicki, M., Yamada, Y., Pereira, A. C. & Krieger, J. E. Meta-analysis of the association of 4 angiotensinogen polymorphisms with essential hypertension. Hypertension 51, 778–783 (2008).
Siffert, W., Rosskopf, D., Siffert, G., Busch, S., Moritz, A., Erbel, R. et al. Association of a human G-protein β3 subunit variant with hypertension. Nat. Genet. 18, 45–48 (1998).
Izawa, H., Yamada, Y., Okada, T., Tanaka, M., Hirayama, H. & Yokota, M. Prediction of genetic risk for hypertension. Hypertension 41, 1035–1040 (2003).
Brand, E., Herrmann, S. M., Nicaud, V., Ruidavets, J. B., Evans, A., Arveiler, D. et al. The 825C/T polymorphism of the G-protein subunit ß3 is not related to hypertension. Hypertension 33, 1175–1178 (1999).
Huang, X., Ju, Z., Song, Y., Zhang, H., Sun, K., Lu, H. et al. Lack of association between the G protein ß3 subunit gene and essential hypertension in Chinese: a case-control and a family-based study. J. Mol. Med. 81, 729–735 (2003).
Snapir, A., Heinonen, P., Tuomainen, T. P., Lakka, T. A., Kauhanen, J., Salonen, J. T. et al. G-protein beta3 subunit C825T polymorphism: no association with risk for hypertension and obesity. J. Hypertens. 19, 2149–2155 (2001).
Bochud, M., Eap, C. B., Elston, R. C., Bovet, P., Maillard, M., Schild, L. et al. Association of CYP3A5 genotypes with blood pressure and renal function in African families. J. Hypertens. 24, 923–929 (2006).
Givens, R. C., Lin, Y. S., Dowling, A. L. S., Thummel, K. E., Lamba, J. K., Schuetz, E. G. et al. CYP3A5 genotype predicts renal CYP3A activity and blood pressure in healthy adults. J. Appl. Physiol. 95, 1297–1300 (2003).
Huyghe, J. R., Fransen, E., Hannula, S., Van Laer, L., Van Eyken, E., Mäki-Torkko, E. et al. A genome-wide analysis of population structure in the Finnish Saami with implications for genetic association studies. Eur. J. Hum. Genet. 19, 347–352 (2011).
Voight, B. F. & Pritchard, J. K. Confounding from cryptic relatedness in case-control association studies. PLoS Genet. 1, e32 (2005).
Fujimoto, A., Kimura, R., Ohashi, J., Omi, K., Yuliwulandari, R., Batubara, L. et al. A scan for genetic determinants of human hair morphology: EDAR is associated with Asian hair thickness. Hum. Mol. Genet. 17, 835–843 (2008).
Ohashi, J., Naka, I., Kimura, R., Natsuhara, K., Yamauchi, T., Furusawa, T. et al. FTO polymorphisms in oceanic populations. J. Hum. Genet. 52, 1031–1035 (2007).
Ohashi, J., Naka, I., Kimura, R., Tokunaga, K., Yamauchi, T., Natsuhara, K. et al. Polymorphisms in the ABO blood group gene in three populations in the New Georgia group of the Solomon Islands. J. Hum. Genet. 51, 407–411 (2006).
Naka, I., Ohashi, J., Kimura, R., Furusawa, T., Yamauchi, T., Nakazawa, M. et al. DRD4 VNTR polymorphism in Oceanic populations. Anthropol. Sci. 120, 151–155 (2012).
Acknowledgements
This study was financially supported by the KAKENHI Grant-in-Aid for Scientific Research of the Ministry of Education, Culture, Sports, Science and Technology, Japan. We thank the people of the Solomon Islands, Tonga and Papua New Guinea for their kind approval and support of our research. We also thank Dr Taniela Palu, at the Diabetes Clinic; Dr Viliami Tangi, the former Minister of Health for the Kingdom of Tonga; and Prof Kazumichi Katayama, at Kyoto University for their cooperation in the study of the Tongan populations. We also thank the chiefs; elders; and church leaders; especially Sir Ikan Rove of the Christian Fellowship Church of the Solomon Islands; and staff of the National Gizo Hospital and Helena Goldie Hospital for their help with the surveys in the Solomon Islands. We are also grateful to the Department of Human Ecology at the University of Tokyo, Japan.
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Furusawa, T., Naka, I., Yamauchi, T. et al. Hypertension-susceptibility gene prevalence in the Pacific Islands and associations with hypertension in Melanesia. J Hum Genet 58, 142–149 (2013). https://doi.org/10.1038/jhg.2012.147
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DOI: https://doi.org/10.1038/jhg.2012.147
