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.
Highlights
Recurrent miscarriage is defined as the loss of two or more consecutive pregnancies before 20 weeks of gestation (Jaslow et al, 2010; Diejomaoh, 2015)
Single-locus analysis suggested that the rs619586 G variant in long non-coding RNA (lncRNA) Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was associated with decreased recurrent miscarriage susceptibility (AG vs. AA: adjusted odds ratios (ORs) = 0.670, 95% confidence intervals (CIs) = 0.457–0.982, p = 0.040; GG vs. AA: adjusted OR = 0.278, 95% confidence intervals (95% CIs) = 0.079– 0.975, p = 0.046; GG/AG vs. AA adjusted OR = 0.621, 95% CI = 0.429–0.900, p = 0.012)
Upon combined analysis of the protective genotypes with regard to the three single nucleotide polymorphisms (SNPs), we found that individuals with two or three protective genotypes exhibited significantly lower recurrent miscarriage risk than those with no or only one protective genotype
Summary
Recurrent miscarriage is defined as the loss of two or more consecutive pregnancies before 20 weeks of gestation (Jaslow et al, 2010; Diejomaoh, 2015). Studies have found that genetic polymorphisms may be involved in the pathogenesis of recurrent miscarriage (Hyde and Schust, 2015), and some cardiovascular disease-related candidate genes have been confirmed to be associated with recurrent miscarriage, such as MTHFR (C677T), APO-E3, and Factor II (G20210A) (El Achi et al, 2018). Studies have confirmed that the expression level of MALAT1 was reduced in the villus samples of recurrent miscarriage patients and the regulation of MALAT1 is one of the factors that contributes to the pathogenesis of recurrent miscarriage (Wang Y. et al, 2018). These studies suggest that the MALAT1 gene polymorphism may be associated with recurrent miscarriage. We investigated whether recurrent miscarriage susceptibility is related to specific MALAT1 gene polymorphisms (rs591291, rs619586, and rs3200401) in a case-control study that included 248 cases and 392 controls from a southern Chinese population
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