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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 .

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