{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T22:01:18Z","timestamp":1779314478766,"version":"3.51.4"},"reference-count":0,"publisher":"Association of Basic Medical Sciences of FBIH","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomol Biomed"],"abstract":"<jats:p>A minority of individuals who consume excessive alcohol develop cirrhosis. Variants in the patatin-like phospholipase domain-containing protein 3 gene (PNPLA3) and the transmembrane 6 superfamily member 2 gene (TM6SF2) have been previously identified as associated with alcohol-related cirrhosis (ALC). This study aimed to examine the variants of PNPLA3\u00a0and\u00a0TM6SF2\u00a0and to develop and assess a polygenic risk score (PRS) for ALC. We enrolled 118 patients diagnosed with ALC and 131 control subjects, who were either abstainers or low-level alcohol consumers without evidence of liver disease. Genotyping of risk variants was performed using PCR-RFLP methodology. PRS, based on independent allelic effect size estimates from genotyped genetic loci, were computed and compared across groups. The development of ALC was significantly associated with CG and GG genotypes of PNPLA3\u00a0(CG: OR: 1.82; 95% CI: 1.05-3.17; p=0.033; GG: OR: 7.64; 95% CI: 3.06-19.07; p&lt;0.001) and the CT genotype of TM6SF2\u00a0(OR: 2.43; 95% CI: 1.27-4.63; p=0.007), controlling for age and sex. Patients with cirrhosis exhibited a significantly higher mean PRS compared to controls (0.32 vs. 0.167, p\u00a0= 1.8e-07). The odds ratios (ORs) and 95% confidence intervals for the group with the highest PRS score compared to the reference group were 6.707; 95% CI: 3.313-13.581, p&lt;0.001. In our ALC patient cohort, the PNPLA3\u00a0rs738409 and TM6SF2\u00a0rs58542926 variants were associated with an increased risk of ALC development. Moreover, the PRS derived from these two variants effectively identified the genetic components linked to cirrhosis within the study population.<\/jats:p>","DOI":"10.17305\/bb.2025.13261","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T23:00:57Z","timestamp":1765580457000},"source":"Crossref","is-referenced-by-count":1,"title":["Genetic risk of alcohol-related liver cirrhosis: Associations of &lt;i&gt;PNPLA3&lt;\/i&gt;, &lt;i&gt;TM6SF2&lt;\/i&gt;, and a two-variant polygenic risk score"],"prefix":"10.17305","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1244-5838","authenticated-orcid":false,"given":"Branka","family":"Nesic","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1344-7867","authenticated-orcid":false,"given":"Marina","family":"Jelovac","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teodora","family":"Karan-Djurasevic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dusica","family":"Vrinic Kalem","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petar","family":"Svorcan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3518-6330","authenticated-orcid":false,"given":"Branka","family":"Zukic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8352-0383","authenticated-orcid":false,"given":"Ivana","family":"Grubisa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"6922","published-online":{"date-parts":[[2025,12,12]]},"container-title":["Biomolecules and Biomedicine"],"original-title":[],"link":[{"URL":"https:\/\/bjbms.org\/ojs\/index.php\/bjbms\/article\/download\/13261\/4080","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bjbms.org\/ojs\/index.php\/bjbms\/article\/download\/13261\/4080","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T23:00:45Z","timestamp":1766703645000},"score":1,"resource":{"primary":{"URL":"https:\/\/bjbms.org\/ojs\/index.php\/bjbms\/article\/view\/13261"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,12]]},"references-count":0,"URL":"https:\/\/doi.org\/10.17305\/bb.2025.13261","relation":{},"ISSN":["2831-090X","2831-0896"],"issn-type":[{"value":"2831-090X","type":"electronic"},{"value":"2831-0896","type":"print"}],"subject":[],"published":{"date-parts":[[2025,12,12]]}}}