Association of twelve polymorphisms in three onco-lncRNA genes with hepatocellular cancer risk and prognosis: A case-control study

Abstract

AIMTo evaluate the association of 12 tag single nucleotide polymorphisms (tagSNPs) in three onco-long non-coding RNA (lncRNA) genes (HOTTIP, CCAT2, MALAT1) with the risk and prognosis of hepatocellular cancer (HCC).METHODSTwelve tagSNPs covering the three onco-lncRNAs were genotyped by the KASP method in a total of 1338 samples, including 521 HCC patients and frequency-matched 817 controls. The samples were obtained from an unrelated Chinese population at the First Hospital of China Medical University from 2012-2015. The expression quantitative trait loci (eQTL) analyses were conducted to explore further the potential function of the promising SNPs.RESULTSThree SNPs in HOTTIP, one promoter SNP in MALAT1, and one haplotype of HOTTIP were associated with HCC risk. The HOTTIP rs17501292, rs2067087, and rs17427960 SNPs were increased to 1.55-, 1.20-, and 1.18-fold HCC risk under allelic models (P = 0.012, 0.017 and 0.049, respectively). MALAT1 rs4102217 SNP was increased to a 1.32-fold HCC risk under dominant models (P = 0.028). In addition, the two-way interaction of HOTTIP rs17501292-MALAT1 rs619586 polymorphisms showed a decreased effect on HCC risk (Pinteraction = 0.028, OR = 0.30) and epistasis with each other. HOTTIP rs3807598 variant genotype showed significantly longer survival time in HBV negative subgroup (P = 0.049, HR = 0.12), and MALAT1 rs591291 showed significantly better prognosis in female and HBV negative subgroups (P = 0.022, HR = 0.37; P = 0.042, HR = 0.25, respectively). In the study, no significant effect was observed in eQTL analysis.CONCLUSIONSpecific lncRNA (HOTTIP and MALAT1) SNPs have potential to be biomarkers for HCC risk and prognosis.

A genetic variant in the promoter of lncRNA MALAT1 is related to susceptibility of ischemic stroke

“…In addition, rs591291 highlighted better prognosis in female and HBV negative subgroups. The association between MALAT1 haplotype (rs4102217-rs591291-rs11227209-rs619586) and HCC risk were not found [25]. In contrast to HCC, we found that A-C-A-G (rs600231-rs1194338-rs4102217-rs591291) haplotype had a 1.3-fold IS risk (Table 4) although SNPs (rs600231, rs4102217, rs591291) did not correlate with IS susceptibility.…”

“…It was reported that genetic variants in the promoter region can affect disease occurrence by involving in transcription efficiency, genetic stability and function [23,24]. At the same time, studies also showed that polymorphisms in MALAT1 affect susceptibility and progression of some diseases [25][26][27], but the impacts on IS have rarely been explored. To date, no study was conducted for the SNPs (rs600231, rs1194338, rs591291 and rs4102217) in promoter of MALAT1 with IS risk.…”

A genetic variant in the promoter of lncRNA MALAT1 is related to susceptibility of ischemic stroke

“…For example, the rs2240183 C allele of lncRNA TUG1 was associated with a higher risk of IS possibly by binding to GATA-1 and elevating TUG1 levels [20], the ANRIL rs2383207 increased the risk of IS by 1.52-fold under the recessive mode [21], the rs217727 TT and rs4929984 AA in the H19 increase the risk of IS, with adjusted OR 4.288, 3.020, respectively [22]. Those provide a new perspective on the genetic mechanism of IS.…”

“…Zhang et al indicated rs4102217 and rs591291 SNPs were not associated with RA susceptibility [35]. Studies of association with HCC have shown rs4102217 had a 1.32-fold risk in the dominant model, and rs591291 highlighted better prognosis in female and HBV negative subgroups, but association between MALAT1 haplotype (rs4102217-rs591291-rs11227209-rs619586) and HCC risk were not found [22]. In our study, we found that A-C-A-G (rs600231-rs1194338-rs4102217-rs591291) haplotype had a 1.3-fold IS risk (Table 4) although SNPs (rs600231, rs4102217, rs591291) did not correlate with IS susceptibility.…”

“…It was reported that genetic variants in the promoter region can affect the expression, subcellular localization, structure stability, and ultimately involve in function and disease progression [21]. At the same time, studies also showed that polymorphisms in MALAT1 affect susceptibility and progression of diseases including hepatocellular cancer, lung adenocarcinoma and pulmonary arterial hypertension [22][23][24], but the impacts on IS have rarely been explored. To date, no study was conducted for the SNPs (rs600231, rs1194338, rs591291 and rs4102217) in promoter of MALAT1 with IS risk.…”