Ser9Gly polymorphism in the dopamine D3 receptor gene is not associated with essential hypertension in the Japanese.
BACKGROUND
The Dopamine D3 receptor (DRD3) gene is thought to be involved in essential hypertension (EH) because dopamine inhibits renin secretion via this receptor and because disruption of the DRD3 gene increases blood pressure in mice. EH is a complex, polygenetic disease. Association studies using the candidate gene approach may provide important clues regarding the etiology of hypertension and define a basis for further genetic investigation. Therefore we examined the association between the Ser9Gly polymorphism in the DRD3 gene and EH.


METHODS
One hundred eighty-one patients with EH and 181 age-matched subjects with normal blood pressure were enrolled. Genomic DNA was extracted from peripheral blood leukocytes. Polymerase chain reaction (PCR) was used to amplify the Ser9Gly polymorphic site in the DRD3 gene, and restriction fragment length polymorphism (RFLP) analysis of the PCR product was used to score the A and G alleles. Plasma renin activity and plasma aldosterone concentration were measured in untreated EH subjects.


RESULTS
The genotype distribution was in Hardy-Weinberg equilibrium, and was not significantly different between the NT and EH groups. The frequencies of A and G alleles were 0.674 (244/362) and 0.326 (118/362) for the NT group and 0.688 (249/362) and 0.312 (113/362) for the EH group, respectively, and did not differ significantly between the two groups. The genotype did not influence the plasma renin activity and aldosterone concentration in untreated EH patients.


CONCLUSIONS
The Ser9Gly polymorphism in the DRD3 gene are not associated with EH. However, our negative result does not exclude the possibility of another variant elsewhere in or near the DRD3 gene in EH.
Soma
Masayoshi
M
2nd Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. msoma@med.nihon-u.ac.jp
Nakayama
Kiyokazu
K
Rahmutula
Dolkun
D
Uwabo
Jiro
J
Sato
Mikano
M
Kunimoto
Masako
M
Aoi
Noriko
N
Kosuge
Kotoko
K
Kanmatsuse
Katsuo
K
D000328:Adult; D000368:Aged; D000483:Alleles; D005260:Female; D005838:Genotype; D005998:Glycine / Q000737:chemistry*; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D007564:Japan; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050637:Receptors, Dopamine D3; D012694:Serine / Q000737:chemistry*
C493593:DRD3 protein, human; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D012694:Serine; D005998:Glycine