SNP-SNP interactions of oncogenic long non-coding RNAs HOTAIR and HOTTIP on gastric cancer susceptibility

Abstract

Genetic variants within oncogenic long non-coding RNAs HOTAIR and HOTTIP may affect their gene expression levels, thereby modifying genetic susceptibility to gastric cancer (GC). In a hospital-based study in Ardabil—a very high-risk area in North-West Iran, 600 blood samples from 300 GC patients and 300 healthy controls were recruited for genotyping. Seven HOTAIR (i.e., rs17720428, rs7958904, rs1899663, and rs4759314) and HOTTIP (i.e., rs3807598, rs17501292, and rs1859168) ‘tag’ single nucleotide polymorphisms (SNPs) were genotyped by the Infinium HTS platform. The rs17720428, rs7958904, and rs1899663 tagSNPs significantly increased GC risk under dominant models by 1.5-, 1.57-, and 1.5-fold, respectively. The G-C-T-A haplotype of HOTAIR tagSNPs increased the risk of GC by 1.31-fold. No significant association was found between HOTTIP SNPs and the risk of GC. HOTAIR and HOTTIP variants were also not associated with any clinicopathologic characteristics. The SNP-SNP interaction of HOTAIR rs17720428/rs7958904 with HOTTIP rs1859168 was associated with an increased risk of GC (rs17720428 TG-rs1859168 CC, OR = 1.76; rs7958904 GC-rs1859168 CC, OR = 1.85; rs7958904 CC-rs1859168 CC, OR = 1.86). Interestingly, the SNP-SNP interaction of HOTAIR rs1899663 with HOTTIP rs1859168 strongly increased the risk of GC (rs1899663 GT-rs1859168 CC, OR = 4.3; rs1899663 TT-rs1859168 CC, OR = 9.37; rs1899663 TT-rs1859168 CA, OR = 6.59). We showed that the HOTAIR rs17720428, rs7958904, and rs1899663 tagSNPs and their interactions with the HOTTIP rs1859168 polymorphism significantly increased the risk of GC. Specifically, novel SNP-SNP interactions between HOTAIR and HOTTIP tagSNPs have a larger impact than individual SNP effects on GC risk, thereby providing us with valuable information to reveal potential biological mechanisms for developing GC.

Polymorphisms in ACE, ACE2, AGTR1 genes and severity of COVID-19 disease

“…Each model provides different assumptions regarding the genetic effect. Using the SNPStats, haplotype frequencies were also obtained for ACE2 and AGTR1 according to the expectation maximization algorithm [25]. Statistical analyses were done by SPSS version 23.0 (IBM, Chicago, USA).…”

Progress of HOTAIR-microRNA in hepatocellular carcinoma

“…For example, the CC genotype of rs920778 polymorphism was significantly associated with breast cancer risk in Turkish population, but no such association was found in Chinese samples [ 82 , 83 ]. Similarly, the T allele of rs12826786 can increase the risk of gastric cancer and adenocarcinoma in Chinese population [ 80 , 84 ]. But the same mutation found in the Turkish population is not associated with genetic susceptibility to gastric cancer, which may be due to differences in race and genetic background [ 78 ].…”

Association between homeobox protein transcript antisense intergenic ribonucleic acid genetic polymorphisms and cholangiocarcinoma

“…Moreover, in a hospital-based case-control study, the rs7958904 HOTAIR SNP was found to increase gastric cancer risk by 1.57-fold. Additionally, the authors reported a possible interaction between HOTAIR rs7958904 and HOTTIP rs1859168 polymorphisms that significantly increased gastric cancer risk[ 39 ]. Similarly, recently rs7958904 G>C has been associated with colorectal cancer prevalence and mortality[ 34 ], and CC rs7958904 genotype has been also linked with increased breast cancer risk compared to the GG homozygo-tes[ 40 ].…”