Phosducin rs12402521 polymorphism predicts development of hypertension in young subjects with overweight or obesity.

Abstract

BACKGROUND AND AIMS:

The G-protein regulator phosducin has been shown to be associated with stress-dependent blood pressure, but whether obesity is a modulator of the relationship between phosducin and risk of hypertension is unknown. We studied the effect of two phosducin polymorphisms on risk of hypertension in 273 overweight or obese (Ov-Ob) young-to-middle-age participants from the HARVEST and 287 normal weight (NW) participants.

METHODS AND RESULTS:

Genotyping of phosducin SNPs rs12402521 and rs6672836 was performed by real time PCR. For rs12402521, 64.6% of the participants were homozygous for the G allele, 27.9% heterozygous, and 7.5% homozygous for the A allele. During 7.7 years of follow-up, 339 subjects developed hypertension. In a Cox multivariable model, carriers of the A allele had a 1.28 (95% CI,1.00-1.63, p = 0.046) increased risk of hypertension. However, increased incidence of hypertension associated with A allele (AA + AG, 79% and GG, 59%, p = 0.001) was observed only among Ov-Ob individuals with a hazard ratio of 1.60 (95% CI, 1.13-2.21, p = 0.007) whereas in NW subjects the incidence of hypertension did not differ by genotype (56% in both groups). In the whole cohort, there was a significant interaction of phosducin genotype with body mass index on the risk of hypertension (p = 0.012). For SNP rs6672836 no association was found with incident hypertension. No haplotype effect was detected on the risk of hypertension.

CONCLUSION:

These data suggest that phosducin rs12402521 polymorphism is an important genetic predictor of obesity-related hypertension. In Ov-Ob carriers of the A allele aggressive nonpharmacological measures should be implemented.

• Authors: P Palatini, G Ceolotto, F Ragazzo, L Mos, M Santonastaso, G Zanata, F Saladini, E Casiglia, HARVEST Study Investigators
• Journal: Nutrition, metabolism, and cardiovascular diseases : NMCD (Nutr Metab Cardiovasc Dis) Vol. 23 Issue 4 Pg. 323-9 (Apr 2013) ISSN: 1590-3729 [Electronic] Netherlands
• PMID: 22365573 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Eye Proteins
• GTP-Binding Protein Regulators
• Phosphoproteins
• phosducin

Topics

• Adult
• Age Factors
• Body Mass Index
• Case-Control Studies
• Chi-Square Distribution
• Disease-Free Survival
• Eye Proteins (genetics)
• Female
• GTP-Binding Protein Regulators (genetics)
• Gene Frequency
• Genetic Predisposition to Disease
• Haplotypes
• Heterozygote
• Homozygote
• Humans
• Hypertension (diagnosis, epidemiology, genetics)
• Incidence
• Italy (epidemiology)
• Kaplan-Meier Estimate
• Logistic Models
• Male
• Multivariate Analysis
• Obesity (diagnosis, epidemiology)
• Overweight (diagnosis, epidemiology)
• Phenotype
• Phosphoproteins (genetics)
• Polymorphism, Genetic
• Proportional Hazards Models
• Real-Time Polymerase Chain Reaction
• Risk Assessment
• Risk Factors
• Time Factors