Association of BET1L and TNRC6B with uterine leiomyoma risk and its relevant clinical features in Han Chinese population

Abstract

Previous studies have shown that uterine leiomyomas (UL) are benign tumours with contributions from environmental and genetic factors. We aimed to replicate two initial significant genetic factors, TNRC6B and BET1L, in a Han Chinese population. A total of 2,055 study subjects were recruited, and 55 SNPs mapped to TNRC6B and BET1L were selected and genotyped in samples from these subjects. Genetic associations were analysed at both the single marker and haplotype levels. Associations between targeted SNPs and relevant clinical features of UL were analysed in case only samples. Functional consequences of significant SNPs were analysed by bioinformatics tools. Two SNPs, rs2280543 from BET1L (χ2 = 18.3, OR = 0.64, P = 1.87 × 10−5) and rs12484776 from TNRC6B (χ2 = 19.7, OR = 1.40, P = 8.91 × 10−6), were identified as significantly associated with the disease status of UL. Rs2280543 was significantly associated with the number of fibroid nodes (P = 0.0007), while rs12484776 was significantly associated with node size (χ2 = 54.88, P = 3.44 × 10−11). Both SNPs were a significant eQTL for their genes. In this study, we have shown that both BET1L and TNRC6B contributed to the risk of UL in Chinese women. Significant SNPs from BET1L and TNRC6B were also identified as significantly associated with the number of fibroid nodes and the size of the node, respectively.

Risk of uterine leiomyoma based on BET1L rs2280543 single nucleotide polymorphism and vegetarian diet

“…Similar to our findings, BET1L rs2280543 was significantly associated with a lower risk of UL among Han Chinese [ 24 ] and European Americans [ 18 , 23 ]. Although this SNP was first reported [ 21 ] and later replicated among Japanese [ 25 ], their findings differed from ours and other findings [ 18 , 23 , 24 ]. This could be due to discrepancies in the reference allele/genotype in the various studies.…”

“…The biological role of BET1L rs2280543 predisposition to UL has been proven by its significant link with BET1L transcription and expression [ 21 , 24 ]. Similar to our findings, BET1L rs2280543 was significantly associated with a lower risk of UL among Han Chinese [ 24 ] and European Americans [ 18 , 23 ].…”

“…The biological role of BET1L rs2280543 predisposition to UL has been proven by its significant link with BET1L transcription and expression [ 21 , 24 ]. Similar to our findings, BET1L rs2280543 was significantly associated with a lower risk of UL among Han Chinese [ 24 ] and European Americans [ 18 , 23 ]. Although this SNP was first reported [ 21 ] and later replicated among Japanese [ 25 ], their findings differed from ours and other findings [ 18 , 23 , 24 ].…”

“…GWAS have identified BET1L rs2280543 as one of the most significant candidate SNPs for UL [ 21 , 23 ]. The association of BET1L rs2280543 polymorphism with UF was initially reported among Japanese women [ 21 ] and later replicated in Han Chinese [ 24 ], European American [ 18 , 23 ], and Japanese women [ 25 ]. However, both variables did not appear to be significantly related among Saudi [ 26 ] and black American women [ 27 ].…”

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

“…BET1L, encoded by BET1L gene, can facilitate the Golgi vesicular membrane trafficking process [33]. However, little is known to date of the biological function of BET1L in IA even though there is a previous report of rs2280543 influencing BET1L expression levels in multiple human tissues [34].…”