{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T06:05:13Z","timestamp":1790057113008,"version":"4.0.1"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Reprod. Health"],"abstract":"<jats:p>\n                    Spontaneous abortion and missed (non-developing) pregnancy are common early reproductive losses in which disturbed folate metabolism and inherited thrombophilia are implicated. Variants of methylenetetrahydrofolate reductase (\n                    <jats:italic>MTHFR<\/jats:italic>\n                    ) and of the plasminogen activator inhibitor-1 gene (\n                    <jats:italic>SERPINE1<\/jats:italic>\n                    \/PAI-1) may increase this risk, but data from Central Asian populations are scarce. We assessed the association of\n                    <jats:italic>MTHFR<\/jats:italic>\n                    rs1801133 (c.665C&amp;gt;T; p.Ala222Val, classically C677T) and the\n                    <jats:italic>SERPINE1<\/jats:italic>\n                    \/PAI-1 \u2212675 4G\/5G promoter insertion\/deletion polymorphism (rs1799889) with early pregnancy loss in a case\u2013control study of ethnic Uzbek women. Eighty-one women with a history of spontaneous abortion (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200940) or missed pregnancy (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200941) and 83 women with a physiologically progressing pregnancy were genotyped. In controls, both loci conformed to Hardy\u2013Weinberg equilibrium. The\n                    <jats:italic>MTHFR<\/jats:italic>\n                    Val allele (40.1% vs. 20.5%) and the Val\/Val genotype (22.2% vs. 3.6%) were significantly more frequent in cases, the mutant homozygote conferring an approximately sevenfold increase in odds (OR 7.6, 95% CI 2.5\u201323.3;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&amp;lt;\u20090.01), whereas the Ala\/Ala genotype was associated with lower odds of loss (OR 0.4). Similarly, the PAI-1 4G allele (46.9% vs. 30.1%) and the 4G\/4G genotype (25.9% vs. 6.0%) were over-represented in cases (4G\/4G: OR 5.5, 95% CI 2.1\u201314.2;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&amp;lt;\u20090.01). Associations were strongest in women with spontaneous abortion. Exploratory ROC analysis indicated moderate, high-specificity discrimination, greatest for the mutant homozygous genotypes (\n                    <jats:italic>MTHFR<\/jats:italic>\n                    Val\/Val AUC 0.69; PAI-1 4G\/4G AUC up to 0.73). In ethnic Uzbek women, the\n                    <jats:italic>MTHFR<\/jats:italic>\n                    Val\/Val and PAI-1 4G\/4G genotypes were associated with spontaneous abortion and missed pregnancy; given the case\u2013control design, these are associations requiring confirmation in larger studies.\n                  <\/jats:p>","DOI":"10.3389\/frph.2026.1943185","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:39:53Z","timestamp":1790055593000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["MTHFR (rs1801133) and SERPINE1\/PAI-1 (\u2212675 4G\/5G) gene polymorphisms and their association with spontaneous abortion and missed pregnancy in an ethnic Uzbek population: a case\u2013control study"],"prefix":"10.3389","volume":"8","author":[{"given":"Farkhod","family":"Akhmedov","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology in Family Medicine, Bukhara State Medical Institute named after Abu Ali Ibn Sino","place":["Bukhara, Uzbekistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulnoza","family":"Axmadjonova","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology No. 2, Andijan State Medical Institute","place":["Andijan, Uzbekistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigora","family":"Axmadaliyeva","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology No. 2, Andijan State Medical Institute","place":["Andijan, Uzbekistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Habibaxon","family":"Negmatshayeva","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology No. 2, Andijan State Medical Institute","place":["Andijan, Uzbekistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saxibaxon","family":"Kasimova","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology No. 2, Andijan State Medical Institute","place":["Andijan, Uzbekistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigina","family":"Nasimova","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology No. 2, Faculty of Pediatrics, Samarkand State Medical University","place":["Samarkand, Uzbekistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"hoad002","DOI":"10.1093\/hropen\/hoad002","article-title":"ESHRE Guideline: recurrent pregnancy loss: an update in 2022","volume":"2023","author":"Bender Atik","year":"2023","journal-title":"Hum Reprod 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