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

Abstract

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.