The lncRNA MALAT1 rs619586 G Variant Confers Decreased Susceptibility to Recurrent Miscarriage

Abstract

Cardiovascula disease and recurrent miscarriage have shared risk factors, and some cardiovascular disease-related candidate genes have been confirmed to be associated with recurrent miscarriage. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA) that is considered to be associated with susceptibility to cardiovascular disease. However, whether lncRNA MALAT1 polymorphisms are related to recurrent miscarriage susceptibility is unclear. We genotyped three lncRNA MALAT1 polymorphisms (rs591291, rs619586, and rs3200401) in 284 patients and 392 controls using TaqMan methods. Logistic regression was used to evaluate the odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for age. Our results showed that the rs619586 G variant had protective effects against recurrent miscarriage (AG vs. AA: adjusted OR = 0.670, 95% CI = 0.457–0.982, p = 0.040; GG vs. AA: adjusted OR = 0.278, 95% CI = 0.079–0.975, p = 0.046; GG/AG vs. AA adjusted OR = 0.621, 95% CI = 0.429–0.900, p = 0.012). In a combined analyses of protective genotypes, with regard to the three single nucleotide polymorphisms (SNPs), we found that individuals with two or three protective genotypes exhibited a significantly lower risk of recurrent miscarriage than those with no or only one protective genotype (adjusted OR = 0.369, 95% CI = 0.199–0.684, p = 0.002). Moreover, the decrease in recurrent miscarriage risk with two or three protective genotypes was most pronounced in women less than 35 years of age (OR = 0.290, 95% CI = 0.142–0.589, p < 0.001) and in women with 2–3 miscarriages (adjusted OR = 0.270, 95% CI = 0.126–0.580, p < 0.001). In conclusion, our study suggests that the rs619586 G variant may have potential protective effects conferring a decreased risk of recurrent miscarriage in the southern Chinese population.

LncRNA HULC Polymorphism Is Associated With Recurrent Spontaneous Abortion Susceptibility in the Southern Chinese Population

“…Recent studies have revealed that some genetic polymorphisms related to immunity-regulation pathways and the regulation of cell motility, such as polymorphisms in IL-1β, p53, IGF-2, and PAI 1, are becoming increasingly important in recurrent spontaneous abortion (Honarvar et al, 2016; Li et al, 2018; Zhu et al, 2018). A recent study conducted by our research group confirmed that polymorphisms in the lncRNAs MALAT1 and CCAT2, which are involved in the regulation of immunity and cell motility, are associated with susceptibility to recurrent spontaneous abortion (Che et al, 2019a; Che et al, 2019b). Therefore, it is important to explore whether polymorphisms in lncRNAs involved in the regulation of immunity and cell motility are associated with susceptibility to recurrent spontaneous abortion, and the results would improve the understanding of the etiology of recurrent spontaneous abortion.…”

“…A study conducted by Wang et al confirmed that MALAT1 is downregulated in patients with recurrent spontaneous abortion, and this downregulated expression is one of the factors leading to the pathogenesis of recurrent spontaneous abortion (Wang et al, 2018). Our previous research also found that MALAT1 polymorphism is associated with susceptibility to recurrent spontaneous abortion (Che et al, 2019b). Similar to the findings obtained for lncRNA MALAT1, many studies have found that the lncRNA HULC is associated with inflammation and cell migration and invasion (Wang et al, 2016; Li et al, 2018).…”

Association of polymorphisms in MALAT1 with the risk of endometrial cancer in Southern Chinese women

“…Rs591291 is a variant of C/T in the exon region of the MALAT1 gene. Che et al found no significant relationship between rs591291 and recurrent miscarriage risk. In our data, we found that there was no relationship in the main effect analysis.…”

Association between the TOX3 rs3803662 C>T polymorphism and recurrent miscarriage in a southern Chinese population

“…27,28 However, it remains unclear whether the TOX3 gene is also associated with recurrent abortion susceptibility, similar to lncRNA CCAT2. 27,28 However, it remains unclear whether the TOX3 gene is also associated with recurrent abortion susceptibility, similar to lncRNA CCAT2.…”

“…and lncRNA MALAT1. 27,28 However, it remains unclear whether the TOX3 gene is also associated with recurrent abortion susceptibility, similar to lncRNA CCAT2. These previous studies suggest that genetic variation in the TOX3 locus may be associated with susceptibility to RM.…”