Background: Recently, fibrillin-1 (FBN1) was reported to play an important role in maintaining the physiological arterial stiffness of essential hypertension (EH). Here, we designed a two-stage case-control study to investigate whether the FBN1 gene harbored any genetic variations associated with EH.
Methods: In stage 1, six candidate single-nucleotide polymorphisms (SNPs) of the FBN1 gene were genotyped and tested in 503 cases and 490 controls. SNPs associated with EH (P < 0.05) in stage 1 would be genotyped in stage 2 (814 cases and 779 controls), and analyzed in all the individuals by allele, genotype, haplotype, and diplotype. A meta-analysis was performed and inverse-variance method with random effect model was employed to estimate combined odds ratio (OR) and its 95% confidence interval (CI) for the identified SNPs.
Results: In stage 1, rs140598 and rs6493333 had statistical association with EH (P < 0.05) and enter stage 2. Multiple logistic regression analysis confirmed that rs140598 but not rs6493333 significantly associated with EH in stage 2 sample. Meta-analysis showed that there was nearly no heterogeneity (I(2) = 0) of genetic variance of rs140598 in the two stages, and the associations of rs140598 in all three genetic models presented statistical significance. Further haplotype analyses showed that the Hap2 (G-C) might decreased the risk of EH when compared with reference haplotype Hap1 (C-C), adjusted OR (95%CI) was 0.823 (0.715-0.948), P = 0.006.
Conclusion: Our finding suggested there is a significant association of rs140598 of FBN1 gene with EH and further replication in other population for association study or prospective study should be warranted.