Two variants in the fibulin2 gene are associated with lower systolic blood pressure and decreased risk of hypertension.
Arterial stiffness is an important factor in hypertension. Fibulin 2 is an extracellular matrix scaffold protein involved in arterial stiffness and, hence, the fibulin 2 (FBLN2) gene may be a candidate for hypertension susceptibility. 4 single nucleotide polymorphisms (SNPs) of FBLN2 were evaluated in an association case-control study containing 447 hypertensive patients and 344 normotensive control subjects. The minor allele frequencies of rs3732666 and rs1061376 were significantly lower in hypertensives. The odds ratios (OR) for having the protective G (rs3732666) and T (rs1061376) alleles were 0.75 (95%CI: 0.58 to 0.96) and 0.83 (95%CI: 0.66 to 1.02), respectively. For rs3732666, the OR for hypertension in AG+GG subjects, compared with AA, was 0.71 (95%CI: 0.52 to 0.95). The protective genotype AG+GG was associated with significantly lower systolic blood pressure (SBP) [-3.6 mmHg (P = 0.048)]. There was a significant age interaction with rs3732666; the effect decreasing with increasing age. For rs1061376, TT subjects had an OR for hypertension of 0.53 (95%CI: 0.32 to 0.87) compared with CC subjects, with reduced SBP (-7.91 mmHg; P = 0.008) and diastolic BP (DBP) (-3.69 mmHg; P = 0.015). The presence of a G allele was an independent predictor of intima-media thickness (IMT); G carrier's having lower mean IMT (-0.037 mm, P = 0.027) compared with AA. Our results provide the first evidence for FBLN2 as a new gene associated with hypertension.
Facultat de Medicina, URLA, Universitat Rovira i Virgili, Hospital Sant Joan, IISPV, CIBERDEM, Reus, Catalonia, Spain. jc.vallve@urv.cat
Joan-Carles
JC
Vallvé
Noemí
N
Serra
Guillermo
G
Zalba
Ana
A
Fortuño
Oscar
O
Beloqui
Raimon
R
Ferre
Josep
J
Ribalta
Lluís
L
Masana
D000704:Analysis of Variance; D001794:Blood Pressure / Q000235:genetics*; D002135:Calcium-Binding Proteins / Q000235:genetics*; D016022:Case-Control Studies; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000453:epidemiology* / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012044:Regression Analysis; D013030:Spain / Q000453:epidemiology; D059289:Vascular Stiffness / Q000235:genetics*; D044465:White People / Q000235:genetics
D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; C084612:fibulin 2