Abstract
We screened DNAs from 48 Japanese individuals for single-nucleotide polymorphisms (SNPs) in eight genes encoding G protein-coupled receptors (GPCRs) by directly sequencing the entire relevant genomic regions except for repetitive-sequence elements. This approach identified 147 SNPs and 31 insertion/deletion polymorphisms among the eight GPCR genes. On average, we identified one SNP in every 584 nucleotides. Of the 147 SNPs, 69 were identified in AGTR1, 12 in AGTR2, nine in AGTRL1, 20 in AVPR1A, nine in AVPR2, 16 in DRD1, six in ITGA2B, and six in PTGIR. Twenty-one SNPs were located in 5' flanking regions, 76 in introns, 32 in exons, and 18 in 3' flanking regions. These variants should contribute to investigations of possible correlations between genotypes and phenotypes as regards susceptibility to disease or responsiveness to drug therapy.
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References
Bichet DG, Oksche A, Rosenthal W (1997) Congenital nephrogenic diabetes insipidus. J Am Soc Nephrol 8:1951–1958
Birnbaumer M, Seibold A, Gilbert S, Ishido M, Barberis C, Antaramian A, Brabet P, Rosenthal W (1992) Molecular cloning of the receptor for human antidiuretic hormone. Nature 357:333–335
Boie Y, Rushmore TH, Darmon-Goodwin A, Grygorczyk R, Slipetz DM, Metters KM, Abramovitz M (1994) Cloning and expression of a cDNA for the human prostanoid IP receptor. J Biol Chem 269:12173–12178
Bonnardeaux A, Davies E, Jeunemaitre X, Fery I, Charru A, Clauser E, Tiret L, Cambien F, Corvol P, Soubrier F (1994) Angiotensin II type 1 receptor gene polymorphisms in human essential hypertension. Hypertension 24:63–69
Cichon S, Nöthen MM, Erdmann J, Propping P (1994) Detection of four polymorphic sites in the human dopamine D1 receptor gene (DRD1). Hum Mol Genet 3:209
Cichon S, Nöthen MM, Stöber G, Schroers R, Albus M, Maier W, Rietschel M, Körner J, Weigelt B, Franzek E, Wildenauer D, Fimmers R, Propping P (1996) Systematic screening for mutations in the 5'-regulatory region of the human dopamine D1 receptor (DRD1) gene in patients with schizophrenia and bipolar affective disorder. Am J Med Genet 67:424–428
Clark D, White FJ (1987) D1 dopamine receptor—the search for a function: a critical evaluation of the D1/D2 dopamine receptor classification and its functional implications. Synapse 1:347–388
Comings DE, Gade R, Wu S, Chiu C, Dietz G, Muhleman D, Saucier G, Ferry L, Rosenthal RJ, Lesieur HR, Rugle LJ, MacMurray P (1997) Studies of potential role of the dopamine D1 receptor gene in addictive behaviors. Mol Psychiatry 2:44–56
Duncan JA, Scholey JW, Miller JA (2001) Angiotensin II type 1 receptor gene polymorphisms in humans: physiology and pathophysiology of the genotypes. Curr Opin Nephrol Hypertens 10:111–116
French DL, Seligsohn U (2000) Platelet glycoprotein IIb-IIIa receptors and Glanzmann's thrombasthenia. Arterioscler Thromb Vasc Biol 20:607–610
Griendling KK, Lassegue B, Alexander RW (1996) Angiotensin receptors and their therapeutic implications. Annu Rev Pharmacol Toxicol 36:281–306
Hein L, Barsh GS, Pratt RE, Dzau VJ, Kobilka BK (1995) Behavioural and cardiovascular effects of disrupting the angiotensin II type-2 receptor in mice. Nature 377:744–747
Heinz A, Sander T, Harms H, Finckh U, Kuhn S, Dufeu P, Dettling M, Graf K, Rolfs A, Rommelspacher H, Schmidt LG (1996) Lack of allelic association of dopamine D1 and D2 (TaqIA) receptor gene polymorphisms with reduced dopaminergic sensitivity to alcoholism. Alcohol Clin Exp Res 20:1109–1113
Hietala J, Pohjalainen T, Heikkila-Kallio U, West C, Salaspuro M, Syvalahti E (1997) Allelic association between D2 but not D1 dopamine receptor gene and alcoholism in Finland. Psychiatr Genet 7:19–25
Hingorani AD, Jia H, Stevens PA, Hopper R, Dickerson JE, Brown MJ (1995) Renin-angiotensin system gene polymorphisms influence blood pressure and the response to angiotensin converting enzyme inhibition. J Hypertens 13:1602–1609
Iida A, Sekine A, Saito S, Kitamura Y, Kitamoto T, Osawa S, Mishima C, Nakamura Y (2001) Catalog of 320 single nucleotide polymorphisms (SNPs) in 20 quinone oxidoreductase and sulfotransferase genes. J Hum Genet 46:225–240
Jard S (1983) Vasopressin: mechanisms of receptor activation. Prog Brain Res 60:383–394
Kainulainen K, Perola M, Terwilliger J, Kaprio J, Koskenvuo M, Syvänen A-C, Vartiainen E, Peltonen L, Kontula K (1999) Evidence for involvement of the type 1 angiotensin II receptor locus in essential hypertension. Hypertension 33:844–849
Katsuya T, Horiuchi M, Minami S, Koike G, Santoro NF, Hsueh AJ, Dzau VJ (1997) Genomic organization and polymorphism of human angiotensin II type 2 receptor: no evidence for its gene mutation in two families of human premature ovarian failure syndrome. Mol Cell Endocrinol 127:221–228
Kikuya M, Sugimoto K, Katsuya T, Suzuki M, Sato T, Funahashi J, Katoh R, Kazama I, Michimata M, Araki T, Hozawa A, Tsuji I, Ogihara T, Yanagisawa T, Imai Y, Matsubara M (2003) A/C1166 gene polymorphism of the angiotensin II type 1 receptor (AT1) and ambulatory blood pressure: the Ohasama Study. Hypertens Res 26:141–145
Kim S-J, Young LJ, Gonen D, Veenstra-VanderWeele J, Courchesne R, Courchesne E, Lord C, Leventhal BL, Cook EH Jr, Insel TR (2002) Transmission disequilibrium testing of arginine vasopressin receptor 1A (AVPR1A) polymorphisms in autism. Mol Psychiatry 7:503–507
Kojima H, Ohmori O, Shinkai T, Terano T, Suzuki T, Abe H (1999) Dopamine D1 receptor gene polymorphism and schizophrenia in Japan. Am J Med Genet 88:116–119
Lankford KL, DeMello FG, Klein WL (1988) D1-type dopamine receptors inhibit growth cone motility in cultured retina neurons: evidence that neurotransmitters act as morphogenic growth regulators in the developing central nervous system. Proc Natl Acad Sci USA 85:4567–4571
Liu Q, Sobell JL, Heston LL, Sommer SS (1995) Screening the dopamine D1 receptor gene in 131 schizophrenics and eight alcoholics: identification of polymorphisms but lack of functionally significant sequence changes. Am J Med Genet 60:165–171
Morello JP, Bichet DG (2001) Nephrogenic diabetes insipidus. Annu Rev Physiol 63:607–630
Nickerson DA, Tobe VO, Taylor SL (1997) PolyPhred: automating the detection and genotyping of single nucleotide substitutions using fluorescence-based resequencing. Nucleic Acids Res 25:2745–2751
O'Dowd BF, Heiber M, Chan A, Heng HH, Tsui LC, Kennedy JL, Shi X, Petronis A, George SR, Nguyen T (1993) A human gene that shows identity with the gene encoding the angiotensin receptor is located on chromosome 11. Gene 136:355–360
Oksche A, Rosenthal W (1998) The molecular basis of nephrogenic diabetes insipidus. J Mol Med 76:326–337
Ono K, Mannami T, Baba S, Yasui N, Ogihara T, Iwai N (2003) Lack of association between angiotensin II type 1 receptor gene polymorphism and hypertension in Japanese. Hypertens Res 26:131–134
Pan Y, Metzenberg A, Das S, Jing B, Gitschier J (1992) Mutations in the V2 vasopressin receptor gene are associated with X-linked nephrogenic diabetes insipidus. Nat Genet 2:103–106
Rana BK, Shiina T, Insel PA (2001) Genetic variations and polymorphisms of G protein-coupled receptors: functional and therapeutic implications. Annu Rev Pharmacol Toxicol 41:593–624
Saito S, Iida A, Sekine A, Eguchi C, Miura Y, Nakamura Y (2001) Seventy genetic variations in human microsomal and soluble epoxide hydrolase genes (EPHX1 and EPHX2) in the Japanese population. J Hum Genet (2001) 46:325–329
Sato M, Soma M, Nakayama T, Kanmatsuse K (2000) Dopamine D1 receptor gene polymorphism is associated with essential hypertension. Hypertension 36:183–186
Schmidt S, Beige J, Walla-Friedel M, Michel MC, Sharma AM, Ritz E (1997) A polymorphism in the gene for the angiotensin II type 1 receptor is not associated with hypertension. J Hypertens 15:1385–1388
Sekine A, Saito S, Iida A, Mitsunobu Y, Higuchi S, Harigae S, Nakamura Y (2001) Identification of single-nucleotide polymorphisms (SNPs) of human N-acetyltransferase genes NAT1, NAT2, AANAT, ARD1, and L1CAM in the Japanese population. J Hum Genet 46:314–319
Small KM, Tanguay DA, Nandabalan K, Zhan P, Stephens JC, Liggett SB (2003) Gene and protein domain-specific patterns of genetic variability within the g-protein coupled receptor superfamily. Am J Pharmacogenomics 3:65–71
Smyth EM, FitzGerald GA (2002) Human prostacyclin receptor. Vitam Horm 65:149–165
Stitham J, Stojanovic A, Hwa J (2002) Impaired receptor binding and activation associated with a human prostacyclin receptor polymorphism. J Biol Chem 277:15439–15444
Stitham J, Stojanovic A, Merenick BL, O'Hara KA, Hwa J (2003) The unique ligand-binding pocket for the human prostacyclin receptor. Site-directed mutagenesis and molecular modeling. J Biol Chem 278:4250–4257
Takami S, Katsuya T, Rakugi H Sato N, Nakata Y, Kamitani A, Miki T, Higaki J, Ogihara T (1998) Angiotensin II type 1 receptor gene polymorphism is associated with increase of left ventricular mass but not with hypertension. Am J Hypertens 11:316–321
Thibonnier M, Graves MK, Wagner MS, Chatelain N, Soubrier F, Corvol P, Willard HF, Jeunemaitre X (2000) Study of V(1)-vascular vasopressin receptor gene microsatellite polymorphisms in human essential hypertension. J Mol Cell Cardiol 32:557–564
Vervoort VS, Beachem MA, Edwards PS, Ladd S, Miller KE, de Mollerat X, Clarkson K, DuPont B, Schwartz CE, Stevenson RE, Boyd E, Srivastava AK (2002) AGTR2 mutations in X-linked mental retardation. Science 296:2401–2403
Wagenaar LJ, Voors AA, Buikema H, van Gilst WH (2002) Angiotensin receptors in the cardiovascular system. Can J Cardiol 18:1331–1339
Wang WY, Zee RY, Morris BJ (1997) Association of angiotensin II type 1 receptor gene polymorphism with essential hypertension. Clin Genet 51:31–34
Whitebread S, Mele M, Kamber B, de Gasparo M (1989) Preliminary biochemical characterization of two angiotensin II receptor subtypes. Biochem Biophys Res Commun 163:284–291
Yamada T, Horiuchi M Dzau VJ (1996) Angiotensin II type 2 receptor mediates programmed cell death. Proc Natl Acad Sci USA 93:156–160
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Saito, S., Iida, A., Sekine, A. et al. Catalog of 178 variations in the Japanese population among eight human genes encoding G protein-coupled receptors (GPCRs). J Hum Genet 48, 461–468 (2003). https://doi.org/10.1007/s10038-003-0062-y
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DOI: https://doi.org/10.1007/s10038-003-0062-y
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