The G protein β3 subunit C825T polymorphism is associated with microalbuminuria in hypertensive women and cardiovascular disease in hypertensive men.
BACKGROUND
The aim of the study was to examine the association between the G protein β3 subunit C825T polymorphism, associated with cardiovascular risk factors like hypertension (HT) and obesity and microalbuminuria (MA), reflecting the endothelial dysfunction in the atherosclerotic process. Second, we wanted to examine the association between the polymorphism and cardiovascular disease (CVD).


METHODS
In the large population-based, cross-sectional Nord-Trøndelag Health Study, HUNT 1995-1997, a total of 5,755 treated hypertensive individuals attended the MA substudy. A randomly selected sample of 1,000 of these was genotyped. A total of 402 men and 540 women were included in the final analyses. MA was measured as albumin/creatinine ratio (ACR) in three urine samples. Logistic regression was used to calculate odds ratios (ORs) for the association between MA or CVD and the genotype.


RESULTS
The study demonstrated a positive association between the TT genotype and MA in women (OR 3.2, 95% confidence interval (CI): 1.1-8.7, P = 0.03), but not in men. The association became stronger with increasing number of positive urine samples and with increasing cutoff value in women with TT genotype compared to the CC genotype. Additionally, there was a positive association between TT genotype and CVD in men and postmenopausal women without hormone therapy.


CONCLUSIONS
Increased MA in TT homozygous women might be explained by other mechanisms of albuminuria or inflammation than the atherosclerotic process. We postulate that the association between CVD and the genotype are mediated through mechanisms other than the classical risk factors and endothelial dysfunction, reflected by MA, which have to be further investigated.
Romundstad
Solfrid
S
HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Verdal, Norway. solfrid.romundstad@ntnu.no
Melien
Oyvind
O
Holmen
Jostein
J
D000368:Aged; D000419:Albuminuria / Q000453:epidemiology / Q000235:genetics*; D000483:Alleles; D001794:Blood Pressure / Q000502:physiology; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D012727:Sex Characteristics
C454420:G-protein beta3 subunit; D004247:DNA; D020962:Heterotrimeric GTP-Binding Proteins