A functional polymorphism in the promoter of TUG1 is associated with an increased risk of ischaemic stroke

et al. 2020

Lipids Health Dis

Background: Metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) was aberrantly expressed in diverse diseases. Particularly in ischemic stroke (IS), the abnormal expression of MALAT1 played important roles including promotion of angiogenesis, inhibition of apoptosis and inflammation and regulation of autophagy. However, the effects of genetic variation (single nucleotide polymorphisms, SNPs) of MALAT1 on IS have rarely been explored. This study aimed to investigate whether SNPs in promoter of MALAT1 were associated with the susceptibility to IS. Methods: A total of 316 IS patients and 320 age-, gender-, and ethnicity-matched controls were enrolled in this study. Four polymorphisms in the promoter of MALAT1 (i.e., rs600231, rs1194338, rs4102217, and rs591291) were genotyped by using a custom-by-design 48-Plex SNPscan kit. Results: The rs1194338 C > A variant in the promoter of MALAT1 was associated with the risk of IS (AC vs.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Wang

et al. 2020

Lipids Health Dis

“…Actually, increasing association studies focused on SNPs of lncRNA involved in process of IS. 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.…”

Section: Discussionmentioning

confidence: 99%

“…Currently, single nucleotide polymorphism (SNP) of lncRNAs have been proved to be associated with IS susceptibility, such as the rs217727 C>T and rs4929984 C>A in lncRNA H19, the rs2240183 C allele in promoter of lncRNA TUG1 [20][21][22]. 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].…”

Section: Introductionmentioning

confidence: 99%

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

wang

et al. 2019

Preprint

Self Cite

Metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) was aberrantly expressed in diverse diseases including ischemic stroke (IS). This study aimed to investigate the association between MALAT1 polymorphism and IS risk. We performed the genotyping of rs600231, rs1194338, rs4102217 and rs591291 in the promoter of MALAT1 by SNPscan method. Quantitative PCR was used to determine the levels of MALAT1 relative expression. We found the rs1194338 C>A variant in MALAT1 promoter was associated with IS risk (AC vs. CC: adjusted OR = 0.623, 95% CI, 0.417-0.932, P = 0.021; AA vs. CC: adjusted OR = 0.474, 95% CI, 0.226-0.991, P = 0.047; AC/AA vs. CC: adjusted OR = 0.596, 95% CI, 0.406-0.874, P = 0.008; A vs. C adjusted OR = 0.658, 95% CI, 0.487-0.890, P = 0.007). The IS patients showed higher expression levels of MALAT1 compared with the control group ( P < 0.05), but patients with AC/AA genotypes of rs1194338 have no significant difference compared to CC genotype ( P > 0.05). In addition, no significant differences were observed in blood lipid levels among SNPs of MALAT1 ( P > 0.05). These results suggest that the rs1194338 AC/AA genotypes may be a protective factor for IS, which mechanism needs to be further explored.

“…Currently, single nucleotide polymorphism (SNP) of lncRNAs have been proved to be associated with IS susceptibility, such as the rs217727 C > T and rs4929984 C > A in lncRNA H19, the rs2240183 C allele in promoter of lncRNA TUG1 [18][19][20]. 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].…”

mentioning

confidence: 99%

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

Wang

et al. 2020

Preprint

Self Cite

Background: Metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) was aberrantly expressed in diverse diseases, and especially plays an important role in nerve injury including promotion of angiogenesis, inhibition of apoptosis and inflammation, regulation of autophagy, which are closely linked to the pathological processes of ischemic stroke (IS). However, the effect of genetic variation (single nucleotide polymorphisms, SNPs) of MALAT1 on IS have rarely been explored. This study aimed to investigate whether polymorphisms in promoter of MALAT1 were associated with the susceptibility to IS. Methods: A total of 316 IS patients and 320 age-, gender-, and ethnicity-matched controls were enrolled in this study. Four polymorphisms in the promoter of MALAT1 (i.e., rsrs600231, rs1194338, rs4102217, and rs591291) were genotyped using a custom‐by‐design 48‐Plex SNPscan kit. Results: The rs1194338 C>A variant in MALAT1 promoter was associated with IS risk (AC vs. CC: adjusted OR = 0.623, 95% CI, 0.417-0.932, P = 0.021; AA vs. CC: adjusted OR = 0.474, 95% CI, 0.226-0.991, P = 0.047; Dominant model: adjusted OR = 0.596, 95% CI, 0.406-0.874, P = 0.008; A vs. C adjusted OR = 0.658, 95% CI, 0.487-0.890, P = 0.007). The Haplotype analysis showed that rs600231-rs1194338-rs4102217-rs591291 (A-C-G-C) had a 1.3-fold increase of IS risk (95% CI, 1.029-1.644, P=0.027). Logistic regression analysis identified some independent impact factors for IS including rs1194338 AC/AA, TC, TG, HDL-C, LDL-C, Apo-A1, Apo-B and NEFA(P < 0.05). Conclusions: These results suggest that the rs1194338 AC/AA genotypes may be a protective factor for IS.