Modulation of blood pressure and obesity with the dopamine D2 receptor gene TaqI polymorphism.
Pharmacological data suggest that obesity and blood pressure (BP) may be modulated through the dopamine D2 receptor (DD2R), which may represent an underlying mechanism that links these conditions. A TAQ:I polymorphism near the DD2R gene has been associated with indices of obesity in white populations. We compared anthropometric and fasting plasma biochemical parameters between 209 nondiabetic hypertensive and 174 gender-matched normotensive Chinese subjects. The hypertensives had increased dyslipidemia, increased fasting plasma glucose concentrations, and a greater degree of obesity. The A1 and A2 alleles of the DD2R gene TAQ:I polymorphism were identified with a polymerase chain reaction-based restriction fragment length polymorphism protocol. The A1 allele frequency was decreased in the hypertensives (42.0%) compared with the control subjects (52.0%, P=0.006), and genotype frequencies were different (P=0.05) between the 2 groups. In the combined population (n=383), systolic, diastolic, and mean arterial BPs were 6, 5, and 6 mm Hg lower, respectively, in subjects with the A1A1 genotype relative to the A2A2 genotype (all P<0.05), whereas skinfold thickness was increased at the iliac (P<0.001) and triceps (P<0.03) sites but not at the biceps or subscapular sites. Furthermore, this DD2R gene polymorphism was shown to be a significant independent predictor of diastolic BP and iliac and triceps skinfold thicknesses (all P<0.03). These contrasting associations of the DD2R TAQ:I polymorphism A1 allele with lower BP but increased markers of "gynoidal" or peripheral subcutaneous obesity (iliac and triceps skinfold thicknesses) in our Chinese population may provide some insight into the underlying relationship between BP and body fat distribution, but the exact nature of this link remains to be determined.
Thomas
G N
GN
Division of Clinical Pharmacology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR. thomas1997@cuhk.edu.hk
Tomlinson
B
B
Critchley
J A
JA
D000328:Adult; D000483:Alleles; D000886:Anthropometry; D001794:Blood Pressure / Q000235:genetics / Q000502:physiology*; D001824:Body Constitution; D015992:Body Mass Index; D004247:DNA / Q000235:genetics / Q000378:metabolism; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000503:physiopathology*; D012150:Polymorphism, Restriction Fragment Length; D017448:Receptors, Dopamine D2 / Q000235:genetics* / Q000378:metabolism; D012885:Skinfold Thickness
D017448:Receptors, Dopamine D2; D004247:DNA; D015252:Deoxyribonucleases, Type II Site-Specific; C027046:TCGA-specific type II deoxyribonucleases