{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T23:04:44Z","timestamp":1762211084945,"version":"build-2065373602"},"reference-count":58,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Faculty of Medicine in Osijek","award":["VIF2017-MEFOS-3","IP26-MEFOS-2025"],"award-info":[{"award-number":["VIF2017-MEFOS-3","IP26-MEFOS-2025"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Premature birth (PTB) is the most common cause of perinatal mortality and morbidity. We performed a case\u2013control study to determine whether two selected single-nucleotide polymorphisms (SNPs) of the progesterone receptor gene (PGR) (rs4754732 and rs653752) play a role in the modulation of the risk for spontaneous PTB. This study included 400 mothers (199 with premature delivery and 201 with term delivery) and 400 newborns (201 term-born and 199 premature-born) of European descent. Genotyping was performed with an ABI PRISM 7500 SDS using TaqMan SNP genotyping assays. We found no statistically significant difference in the distribution of genotypes and allele frequencies between prematurely born newborns and newborns at term for either investigated SNP. There was no statistically significant difference in the distribution of genotypes and allele frequencies between groups of mothers with extremely early and early PTB compared to the group of mothers with term births. Potential association of the mothers\u2019 C allele of rs653752 with lower odds of PTB (p = 0.03; odds ratio 1.36; 95% confidence interval 1.02\u20131.81; Chi-square test), and association of the mothers\u2019 CC genotype of rs653752 in the recessive inheritance model with lower odds of PTB in general (p = 0.02; odds ratio 0.54; 95% confidence interval 0.32\u20130.91; Chi-square test) and with a late PTB (p = 0.005, odds ratio 0.45, 95% confidence interval 0.23\u20130.79; Chi-square test), were found. It was also found that the mothers who were carriers of the haplotype T-G combination of rs4754732 and rs653752 were 1.5 times more likely to have PTB, even after correcting the p-value for multiple comparisons (p = 0.008; odds ratio 1.59; 95% confidence interval 1.13\u20132.24, Chi-square test). Further research on a larger number of subjects of these and other PGR SNPs will be needed in order to confirm the presented results.<\/jats:p>","DOI":"10.3390\/ijms26041606","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T12:06:32Z","timestamp":1739448392000},"page":"1606","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Variants of the Progesterone Receptor Gene as Modulators of Risk for Idiopathic Spontaneous Premature Birth"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3005-4571","authenticated-orcid":false,"given":"Mirta","family":"Kadivnik","sequence":"first","affiliation":[{"name":"Clinic of Obstetrics and Gynecology, University Hospital Center Osijek, J. Huttlera 4, 31000 Osijek, Croatia"},{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, J.J. Strossmayer University, 31000 Osijek, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2424-6518","authenticated-orcid":false,"given":"Marija","family":"Dundovi\u0107","sequence":"additional","affiliation":[{"name":"Clinic of Obstetrics and Gynecology, University Hospital Center Osijek, J. Huttlera 4, 31000 Osijek, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreja","family":"Bartuli\u0107","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University Hospital Center Osijek, 31000 Osijek, Croatia"},{"name":"Department of Internal Medicine, Faculty of Medicine, J.J. Strossmayer University, 31000 Osijek, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vinka","family":"Rup\u010di\u0107 Rubin","sequence":"additional","affiliation":[{"name":"Clinic of Obstetrics and Gynecology, University Hospital Center Osijek, J. Huttlera 4, 31000 Osijek, Croatia"},{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, J.J. Strossmayer University, 31000 Osijek, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristina","family":"Abi\u010di\u0107 \u017duljevi\u0107","sequence":"additional","affiliation":[{"name":"Clinic of Obstetrics and Gynecology, University Hospital Center Osijek, J. Huttlera 4, 31000 Osijek, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iva","family":"Mili\u0107 Vranje\u0161","sequence":"additional","affiliation":[{"name":"Clinic of Obstetrics and Gynecology, University Hospital Center Osijek, J. Huttlera 4, 31000 Osijek, Croatia"},{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, J.J. Strossmayer University, 31000 Osijek, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4481-6365","authenticated-orcid":false,"given":"Kristina","family":"Kralik","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics and Informatics, Faculty of Medicine, J.J. Strossmayer University, 31000 Osijek, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nena","family":"Arvaj","sequence":"additional","affiliation":[{"name":"Department of Medical Biology and Genetics, Faculty of Medicine, J.J. Strossmayer University, 31000 Osijek, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1126-7523","authenticated-orcid":false,"given":"Jasenka","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Medical Biology and Genetics, Faculty of Medicine, J.J. Strossmayer University, 31000 Osijek, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,13]]},"reference":[{"key":"ref_1","unstructured":"World Health Organisation (2014). Born Too Soon: The Global Action Report on Preterm Birth, WHO. Available online: https:\/\/www.who.int\/publications\/i\/item\/9789241503433."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6047","DOI":"10.1016\/j.vaccine.2016.03.045","article-title":"Preterm Birth: Case Definition and Guidelines for Data Collection, Analysis, and Presentation of Immunisation Safety Data","volume":"34","author":"Quinn","year":"2016","journal-title":"Vaccine"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1016\/S0140-6736(23)00878-4","article-title":"National, Regional, and Global Estimates of Preterm Birth in 2020, with Trends from 2010: A Systematic Analysis","volume":"402","author":"Ohuma","year":"2023","journal-title":"Lancet"},{"key":"ref_4","first-page":"S37","article-title":"Perinatalni Mortalitet u Republici Hrvatskoj u 2015. Godini","volume":"25","author":"Juras","year":"2017","journal-title":"Gynaecol. Perinatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.siny.2004.04.002","article-title":"Epidemiology of Preterm Birth and Neonatal Outcome","volume":"9","author":"Wen","year":"2004","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1055\/s-2006-956771","article-title":"Myometrial Progesterone Responsiveness","volume":"25","author":"Mesiano","year":"2007","journal-title":"Semin. Reprod. Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Yellon, S.M., Dobyns, A.E., Beck, H.L., Kurtzman, J.T., Garfield, R.E., and Kirby, M.A. (2013). Loss of Progesterone Receptor-Mediated Actions Induce Preterm Cellular and Structural Remodeling of the Cervix and Premature Birth. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0081340"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1126\/science.1251816","article-title":"Preterm Labor: One Syndrome, Many Causes","volume":"345","author":"Romero","year":"2014","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"520.e1","DOI":"10.1016\/j.ajog.2015.06.014","article-title":"Progesterone Inhibits In Vitro Fetal Membrane Weakening","volume":"213","author":"Kumar","year":"2015","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1177\/1933719107310990","article-title":"Single Nucleotide Polymorphisms in the Human Progesterone Receptor Gene and Spontaneous Preterm Birth","volume":"15","author":"Luo","year":"2008","journal-title":"Reprod. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.ajog.2017.11.576","article-title":"Vaginal Progesterone for Preventing Preterm Birth and Adverse Perinatal Outcomes in Singleton Gestations with a Short Cervix: A Meta-Analysis of Individual Patient Data","volume":"218","author":"Romero","year":"2018","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"135.e1","DOI":"10.1016\/j.ajog.2011.03.048","article-title":"Progesterone Receptor Polymorphisms and Clinical Response to 17-Alpha-Hydroxyprogesterone Caproate","volume":"205","author":"Manuck","year":"2011","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.ijgo.2008.08.029","article-title":"Oral Micronized Progesterone for Prevention of Preterm Birth","volume":"104","author":"Rai","year":"2009","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3831","DOI":"10.1016\/j.jmb.2016.06.020","article-title":"Progesterone Receptor Signaling Mechanisms","volume":"428","author":"Grimm","year":"2016","journal-title":"J. Mol. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6773","DOI":"10.1111\/jcmm.16681","article-title":"Pro-Inflammatory Signals Induce 20\u03b1-HSD Expression in Myometrial Cells: A Key Mechanism for Local Progesterone Withdrawal","volume":"25","author":"Nadeem","year":"2021","journal-title":"J. Cell Mol. Med."},{"key":"ref_16","first-page":"188","article-title":"Progesterone Action in the Myometrium and Decidua in Preterm Birth","volume":"4","author":"Blanks","year":"2012","journal-title":"Facts Views Vis. ObGyn"},{"key":"ref_17","first-page":"5236","article-title":"A Functional Polymorphism in the Progesterone Receptor Gene Is Associated with an Increase in Breast Cancer Risk","volume":"63","author":"Hankinson","year":"2003","journal-title":"Cancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1002\/j.1460-2075.1990.tb08280.x","article-title":"Two Distinct Estrogen-Regulated Promoters Generate Transcripts Encoding the Two Functionally Different Human Progesterone Receptor Forms A and B","volume":"9","author":"Kastner","year":"1990","journal-title":"EMBO J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"a023127","DOI":"10.1101\/cshperspect.a023127","article-title":"Genomics of Preterm Birth","volume":"5","author":"Swaggart","year":"2015","journal-title":"Cold Spring Harb. Perspect Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1093\/aje\/kwt005","article-title":"Fetal and Maternal Genes\u2019 Influence on Gestational Age in a Quantitative Genetic Analysis of 244,000 Swedish Births","volume":"178","author":"York","year":"2013","journal-title":"Am. J. Epidemiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.ajog.2013.10.001","article-title":"The Contribution of Genetic and Environmental Factors to the Duration of Pregnancy","volume":"210","author":"York","year":"2014","journal-title":"Am. J Obstet. Gynecol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1093\/aje\/kwp328","article-title":"Maternal Effects for Preterm Birth: A Genetic Epidemiologic Study of 630,000 Families","volume":"170","author":"Svensson","year":"2009","journal-title":"Am. J. Epidemiol."},{"key":"ref_23","unstructured":"(2024, December 20). GeneCards. Available online: https:\/\/www.genecards.org\/cgi-bin\/carddisp.pl?gene=PGR."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.mrrev.2008.05.001","article-title":"Discovery and Verification of Functional Single Nucleotide Polymorphisms in Regulatory Genomic Regions: Current and Developing Technologies","volume":"659","author":"Chorley","year":"2008","journal-title":"Mutat. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"S273","DOI":"10.1186\/ar555","article-title":"Single Nucleotide Polymorphisms and Disease Gene Mapping","volume":"4","author":"Bell","year":"2002","journal-title":"Arthritis. Res."},{"key":"ref_26","first-page":"69570","article-title":"Sudan Comprehensive Analysis of RsSNPs Associated with Hypertension Using In-Silico Bioinformatics Tools","volume":"3","author":"Gassoum","year":"2016","journal-title":"Open Access Libr. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1038\/s41586-020-2528-x","article-title":"Global Reference Mapping of Human Transcription Factor Footprints","volume":"583","author":"Vierstra","year":"2020","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1126\/science.1222794","article-title":"Systematic Localization of Common Disease-Associated Variation in Regulatory DNA","volume":"337","author":"Maurano","year":"2012","journal-title":"Science"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1203\/PDR.0b013e3181567bfc","article-title":"Evaluation of Fetal and Maternal Genetic Variation in the Progesterone Receptor Gene for Contributions to Preterm Birth","volume":"62","author":"Ehn","year":"2007","journal-title":"Pediatr. Res."},{"key":"ref_30","first-page":"271","article-title":"The Progesterone Receptor Gene Polymorphism as Factor of Risk for the Preterm Delivery","volume":"33","author":"Oliveira","year":"2011","journal-title":"Rev. Bras. Ginecol. Obs."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/jp.2012.118","article-title":"Polymorphisms in the fetal progesterone receptor and a calcium-activated potassium channel isoform are associated with preterm birth in an Argentinian population","volume":"33","author":"Mann","year":"2013","journal-title":"J. Perinatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"369.e1","DOI":"10.1016\/j.ajog.2017.05.019","article-title":"The Association among Cytochrome P450 3A, Progesterone Receptor Polymorphisms, Plasma 17-Alpha Hydroxyprogesterone Caproate Concentrations, and Spontaneous Preterm Birth","volume":"217","author":"Bustos","year":"2017","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.mgene.2014.12.002","article-title":"MTHFR (C677T) Polymorphism and PR (PROGINS) Mutation as Genetic Factors for Preterm Delivery, Fetal Death and Low Birth Weight: A Northeast Indian Population-Based Study","volume":"3","author":"Tiwari","year":"2015","journal-title":"Meta Gene"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1590\/SO100-720320150005338","article-title":"Suscetibilidade \u00e0 Prematuridade: Investiga\u00e7\u00e3o de Fatores Comportamentais, Gen\u00e9ticos, M\u00e9dicos e Sociodemogr\u00e1ficos","volume":"37","author":"Hackbarth","year":"2015","journal-title":"Rev. Bras. Gynecol. Obstet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"E719","DOI":"10.1210\/jc.2011-3251","article-title":"Progesterone Receptor-A and -B Have Opposite Effects on Proinflammatory Gene Expression in Human Myometrial Cells: Implications for Progesterone Actions in Human Pregnancy and Parturition","volume":"7","author":"Tan","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1111\/jog.15194","article-title":"Progesterone Receptor Genetic Variants in Pregnant Women and Fetuses as Possible Predictors of Spontaneous Premature Birth: A Preliminary Case-Control Study","volume":"48","author":"Kadivnik","year":"2022","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.bpobgyn.2018.04.003","article-title":"The Global Epidemiology of Preterm Birth","volume":"52","author":"Vogel","year":"2018","journal-title":"Best. Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"31","DOI":"10.2471\/BLT.08.062554","article-title":"The Worldwide Incidence of Preterm Birth: A Systematic Review of Maternal Mortality and Morbidity","volume":"88","author":"Beck","year":"2010","journal-title":"Bull. World Health Organ."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1093\/aje\/kwp324","article-title":"Maternal Contributions to Preterm Delivery","volume":"170","author":"Boyd","year":"2009","journal-title":"Am. J. Epidemiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/S0029-7844(97)00215-9","article-title":"The Risk of Preterm Birth across Generations","volume":"90","author":"Porter","year":"1997","journal-title":"Obstetr. Gynecol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.ajog.2017.12.009","article-title":"Spontaneous Preterm Birth: Advances toward the Discovery of Genetic Predisposition","volume":"218","author":"Strauss","year":"2018","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_42","first-page":"1156","article-title":"A Genome-Wide Association Study of Early Spontaneous Preterm Delivery","volume":"377","author":"Zhang","year":"2015","journal-title":"Genet. Epidemiol."},{"key":"ref_43","first-page":"125","article-title":"Progesterone Receptor Localization and Isoforms in Myometrium, Decidua, and Fetal Membranes from Rhesus Macaques: Evidence for Functional Progesterone Withdrawal at Parturition","volume":"9","author":"Haluska","year":"2002","journal-title":"J. Soc. Gynecol. Investig."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1196\/annals.1335.004","article-title":"Mechanisms Underlying \u201cFunctional\u201d Progesterone Withdrawal at Parturition","volume":"1034","author":"Brown","year":"2004","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1210\/me.2005-0242","article-title":"Up-Regulation of the Progesterone Receptor (PR)-C Isoform in Laboring Myometrium by Activation of Nuclear Factor-\u039aB May Contribute to the Onset of Labor through Inhibition of PR Function","volume":"20","author":"Condon","year":"2006","journal-title":"Mol. Endocrinol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1007\/s10549-013-2592-0","article-title":"Association of Progesterone Receptor Gene (PGR) Variants and Breast Cancer Risk in African American Women","volume":"139","author":"Gabriel","year":"2013","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1177\/1933719110382922","article-title":"Progesterone Receptors in the Human Pregnancy Uterus: Do They Hold the Key to Birth Timing?","volume":"18","author":"Mesiano","year":"2011","journal-title":"Reprod. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"95","DOI":"10.2147\/BCTT.S123785","article-title":"An Exploratory Study of Host Polymorphisms in Genes That Clinically Characterize Breast Cancer Tumors and Pretreatment Cognitive Performance in Breast Cancer Survivors","volume":"9","author":"Koleck","year":"2017","journal-title":"Breast Cancer Targets Ther."},{"key":"ref_49","unstructured":"Kadivnik, M. (2022). Progesterone Receptor Gene Polymorphisms in the Modulation of Risk for Idiopathic Spontaneous Premature Birth. [Ph.D. Thesis, Medical Faculty in Osijek, Josip Juraj Strossmayer University in Osijek]."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2762","DOI":"10.1093\/humrep\/17.10.2762","article-title":"Fetal Sex and Preterm Birth: Are Males at Greater Risk?","volume":"17","author":"Zeitlin","year":"2002","journal-title":"Hum. Reprod."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.earlhumdev.2003.10.006","article-title":"Offspring Sex and Pregnancy Outcome by Length of Gestation","volume":"76","author":"Vatten","year":"2004","journal-title":"Early Hum. Dev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1177\/1933719117718270","article-title":"The Burden of Genetic and Epigenetic Traits in Prematurity","volume":"25","year":"2018","journal-title":"Reprod. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1111\/jcpp.12114","article-title":"Gene-Environment Interactions in Genome-Wide Association Studies: Current Approaches and New Directions","volume":"54","author":"Winham","year":"2013","journal-title":"J. Child. Psychol. Psychiatry"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1111\/j.1471-0528.2002.01068.x","article-title":"Algorithms for Combining Menstrual and Ultrasound Estimates of Gestational Age: Consequences for Rates of Preterm and Postterm Birth","volume":"109","author":"Blondel","year":"2002","journal-title":"BJOG"},{"key":"ref_55","unstructured":"Applied Biosystems (2010). 7500\/7500 Fast Real-Time PCR System: Genotyping Experiments, Applied Biosystems."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/978-1-61779-842-9_10","article-title":"Genotyping of Single Nucleotide Polymorphisms by 5\u2032 Nuclease Allelic Discrimination","volume":"882","author":"Malkki","year":"2012","journal-title":"Methods Mol. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.1093\/bioinformatics\/btl268","article-title":"SNPStats: A web tool for the analysis of association studies","volume":"22","author":"Valls","year":"2006","journal-title":"Bioinformatics"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"(2013). World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. JAMA, 310, 2191\u20132194.","DOI":"10.1001\/jama.2013.281053"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/4\/1606\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:33:51Z","timestamp":1760027631000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/4\/1606"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,13]]},"references-count":58,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["ijms26041606"],"URL":"https:\/\/doi.org\/10.3390\/ijms26041606","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,2,13]]}}}