FAILURE TO REPLICATE THE ASSOCIATION OF UROMODULIN GENE VARIANT RS 13333226 WITH HYPERTENSION IN A GENERAL POPULATION STUDY

Objective: A recent GWAS study of blood pressure (BP) extremes identified a strong association with hypertension of an A/G polymorphic variant (rs13333226) of the UMOD gene encoding uromodulin, the less common G-allele being associated with lower BP. Aim of the present study was to investigate the consistency of this association in a sample of Italian general population (VOBARNO Study) characterized by repeated clinical (CLIN) and ambulatory BP (ABPM) measurements over a decade. Design and Methods: Genotyping of rs13333226 was performed using the TaqMan assay. Genotype data are available in 525 subjects (238 males, aged 50.4 ± 8.2, BMI 25.7 ± 3.8; mean ± SD) at the time of study entry (BAS) and in 429 at a second follow-up evaluation (FU), after an average of 8.7 years Hypertension was defined as BP values ≥140/90 and/or ≥125/80, respectively at CLIN and ABPM, or in presence of antihypertensive drug treatment. In addition, association of rs13333226 with renal function (eGFR, urinary albumin excretion), metabolic risk factors (cholesterol, glycemia, uric acid), cardiovascular damage (left ventricular hypertrophy, carotid intima media thickening) and cardiovascular events were also investigated. Results: Genotype distribution (AA 74%, AG 23%, GG 3%) resulted in Hardy-Weinberg equilibrium; G-allele frequency (0.14) was slightly lower than in previous reports. At univariate analysis there was a trend toward slightly higher BP values in G-allele carriers both at CLIN and ABPM measurements and at BAS and FU evaluations. The same was found when hypertension was considered as a dichotomic variable and when treated subjects were excluded from the analysis. After adjustment for age, sex and BMI, the presence of at least one copy of the G-allele was weakly associated with hypertension at FU evaluation (OR 1.69, 95%CI 1.00–2.87, p = 0.05). No significant association of rs13333226 with the other phenotypes examined was detected. Conclusion: Despite careful genotyping and BP phenotyping, we were not able to replicate, in this sample of general population, the previously described association of UMOD SNP rs13333226 G-allele with lower BP values and we found, if any, an opposite trend.