Replication of GWAS Loci Revealed an Increased Risk of BET1L and H19 Polymorphisms with Intracranial Aneurysm

Abstract EN

A genome-wide association study (GWAS) identified that BET1L rs2280543 at chromosome 11p15.5 was a susceptibility loci of intracranial aneurysm (IA).

Long noncoding RNA H19, located in this region, was reported to play a crucial role in the formation of IA.

In this study, we aimed to examine whether BET1L rs2280543 and potentially functional polymorphisms in H19 influence the risk of IA.

A hospital-based case-control study was performed involving 542 IA patients and 588 age- and gender-matched controls.

The BET1L rs2280543 and H19 polymorphisms were genotyped using the TaqMan assay.

The BET1L rs2280543 CT, CT/TT genotypes, and T allele were associated with an increased risk of IA (CT vs.

CC, adjusted OR=1.43, 95% CI: 1.08-1.90, P=0.01; CT/TT vs.

CC, adjusted OR=1.48, 95% CI: 1.12-1.94, P=0.005; and T vs.

C, adjusted OR=1.44, 95% CI: 1.13-1.83, P=0.003).

Similarly, the H19 rs217727 TT genotype and T allele were associated with an increased risk of IA (TT vs.

CC, adjusted OR=1.90, 95% CI: 1.35-2.67, P<0.001; T vs.

C, adjusted OR=1.38, 95% CI: 1.16-1.64, P<0.001).

Combined analyses revealed that the rs2280543 CC-rs217727 CT/TT, rs2280543 CT/TT-rs2735971 GG, and rs217727 CT/TT-rs2735971 GG genotypes were related to the risk of IA.

Interaction analysis showed that the 3-loci model of rs2280543-rs217727-rs2839698 contributed to an increased risk of IA.

These findings suggest that the GWAS-discovered risk loci BET1L rs2280543 may increase IA susceptibility by interacting with lncRNA H19.