title: Phosducin rs12402521 polymorphism predicts development of hypertension in young subjects with overweight or obesity.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Clinical and Experimental Medicine, Clinica Medica 4, University of Padova, Via Giustiniani 2, 35128 Padova, Italy. palatini@unipd.it
authors.forename: P
authors.initials: P
authors.lastname: Palatini
authors.forename: G
authors.initials: G
authors.lastname: Ceolotto
authors.forename: F
authors.initials: F
authors.lastname: Ragazzo
authors.forename: L
authors.initials: L
authors.lastname: Mos
authors.forename: M
authors.initials: M
authors.lastname: Santonastaso
authors.forename: G
authors.initials: G
authors.lastname: Zanata
authors.forename: F
authors.initials: F
authors.lastname: Saladini
authors.forename: E
authors.initials: E
authors.lastname: Casiglia
mesh_terms: D000328:Adult; D000367:Age Factors; D015992:Body Mass Index; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D020555:GTP-Binding Protein Regulators / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D009765:Obesity / Q000175:diagnosis / Q000453:epidemiology*; D050177:Overweight / Q000175:diagnosis / Q000453:epidemiology*; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
chemical_list: D005136:Eye Proteins; D020555:GTP-Binding Protein Regulators; D010750:Phosphoproteins; C065631:phosducin