{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T04:12:04Z","timestamp":1777954324348,"version":"3.51.4"},"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosglobalpublichealth.org"],"crossmark-restriction":false},"short-container-title":["PLOS Glob Public Health"],"abstract":"\n Lactose intolerance is a complex symptomatic response to lactose maldigestion that is influenced by, but not strictly determined by, the down- regulation of the enzyme lactase. Several nucleotide polymorphisms\u2009\n \u2212\u200913910C\u2009>\u2009T (rs4988235),\u2009\u2212\u200913907C\u2009>\u2009G (rs41525747),\u2009\u2212\u200913915T\u2009>\u2009G (rs41380347),\u2009\u2212\u200914010G\u2009>\u2009C (rs145946881)<\/jats:italic>\n \n and \u221214009T\u2009>\u2009G<\/jats:italic>\n <\/jats:bold>\n (rs869051967)<\/jats:italic>\n upstream of the LCT gene have been associated with lactase persistence in European, African and Middle Eastern populations. We aimed to study the prevalence of lactase-persistence associated variants of the LCT gene in the Libyan population and its correlation with digestive symptoms (heartburn, diarrhea, nausea, bloating, abdominal cramps,).Buccal DNA swabs were collected from 242 adult individuals from the western, southern and eastern regions of Libya. A 500 bp DNA region spanning the\u2009\n \u2212\u200913910C\u2009>\u2009T<\/jats:italic>\n variant was analyzed. Novel variants (-13883T\u2009>\u2009A, -13921A\u2009>\u2009C, -13961T\u2009>\u2009C and -13962C\u2009>\u2009A) were detected in the analyzed region in addition to the previously described\u2009\n \u2212\u200913910C\u2009>\u2009T<\/jats:italic>\n and\n \u221213915T\u2009>\u2009G<\/jats:italic>\n variants. However, their functional impact on lactase expression remains to be determined. The prevalence of the lactase persistence phenotype was associated with the derived alleles \u2212\n 13910*T<\/jats:italic>\n and\n \u221213915*G<\/jats:italic>\n , which were collectively detected in 30% of the study participants. The allele frequency of the lactase persistence -13915*G variant was 0.133 (SD\u2009\u00b1\u20090.016), whereas the frequency of the -13910*T allele was 0.029 (SD\u2009\u00b1\u20090.008). The most common was the Arab variant\u2009\n \u2212\u200913915T\u2009>\u2009G<\/jats:italic>\n in the eastern region of Libya followed by the European\u2009\n \u2212\u200913910C\u2009>\u2009T<\/jats:italic>\n variant. Both novel and well-known variants of LCT gene associated with lactase persistence are common in Libyans. Further studies are needed to confirm the association of the novel discovered variants with lactase persistence.\n <\/jats:p>","DOI":"10.1371\/journal.pgph.0006386","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T17:43:52Z","timestamp":1777916632000},"page":"e0006386","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgph.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Community based countrywide analysis of lactase persistence related genetic variants and their correlation with digestive symptoms in Libya"],"prefix":"10.1371","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9678-2243","authenticated-orcid":true,"given":"Ariej M.","family":"Mustafa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3371-0215","authenticated-orcid":true,"given":"Inas M.","family":"Alhudiri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdenaser A.","family":"Mohamed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hafsa","family":"Al-Emam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7510-1063","authenticated-orcid":true,"given":"Ahmad","family":"Ramadan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4100-6743","authenticated-orcid":true,"given":"Halla","family":"Elshwekh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamza","family":"Ben Zeglam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nabil S.","family":"Enattah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"issue":"2","key":"pgph.0006386.ref001","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1042\/bj2410427","article-title":"Biosynthesis and maturation of lactase-phlorizin hydrolase in the human small intestinal epithelial cells","volume":"241","author":"HY Naim","year":"1987","journal-title":"Biochem J"},{"issue":"6","key":"pgph.0006386.ref002","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1016\/S0016-5085(98)70429-9","article-title":"The genetically programmed down-regulation of lactase in children","volume":"114","author":"Y Wang","year":"1998","journal-title":"Gastroenterology"},{"key":"pgph.0006386.ref003","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1146\/annurev.genet.37.110801.143820","article-title":"Genetics of lactase persistence and lactose intolerance","volume":"37","author":"DM Swallow","year":"2003","journal-title":"Annu Rev Genet"},{"key":"pgph.0006386.ref004","doi-asserted-by":"crossref","DOI":"10.1016\/B978-0-12-811720-0.00001-5","article-title":"The evolution of lactose digestion.","author":"C Walker","year":"2019","journal-title":"Lactose: Evolutionary role, health effects, and applications. Elsevier"},{"key":"pgph.0006386.ref005","volume-title":"Molecular genetics of lactase persistence","author":"NS Enattah","year":"2005"},{"key":"pgph.0006386.ref006","first-page":"18","article-title":"Lactose intolerance: from diagnosis to correct management","volume":"17","author":"T Di Rienzo","year":"2013","journal-title":"European review for medical and pharmacological sciences"},{"key":"pgph.0006386.ref007","doi-asserted-by":"crossref","DOI":"10.1093\/hmg\/ddab027","article-title":"Human adaptation, demography and cattle domestication: an overview of the complexity of lactase persistence in Africa","volume":"30","author":"MC Campbell","year":"2021","journal-title":"Hum Mol Genet"},{"issue":"13","key":"pgph.0006386.ref008","doi-asserted-by":"crossref","DOI":"10.1016\/j.heliyon.2024.e33455","article-title":"Lactase persistence in the Jordanian population: Potential effects of the Arabian Peninsula and Sahara\u2019s aridification","volume":"10","author":"AK Alkaraki","year":"2024","journal-title":"Heliyon"},{"issue":"9","key":"pgph.0006386.ref009","doi-asserted-by":"crossref","first-page":"2705","DOI":"10.1002\/j.1460-2075.1988.tb03124.x","article-title":"Complete primary structure of human and rabbit lactase-phlorizin hydrolase: implications for biosynthesis, membrane anchoring and evolution of the enzyme","volume":"7","author":"N Mantei","year":"1988","journal-title":"EMBO J"},{"key":"pgph.0006386.ref010","doi-asserted-by":"crossref","first-page":"26","DOI":"10.3109\/00365529409091742","article-title":"Diagnosis of hypolactasia and lactose malabsorption","volume":"202","author":"H Arola","year":"1994","journal-title":"Scand J Gastroenterol Suppl"},{"issue":"2","key":"pgph.0006386.ref011","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1093\/ajcn\/nqz104","article-title":"Lactose digestion in humans: intestinal lactase appears to be constitutive whereas the colonic microbiome is adaptable","volume":"110","author":"RA Forsg\u00e5rd","year":"2019","journal-title":"Am J Clin Nutr"},{"issue":"3","key":"pgph.0006386.ref012","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/j.ajcnut.2023.12.016","article-title":"Changes in gut microbiota and lactose intolerance symptoms before and after daily lactose supplementation in individuals with the lactase nonpersistent genotype","volume":"119","author":"L JanssenDuijghuijsen","year":"2024","journal-title":"Am J Clin Nutr"},{"issue":"4","key":"pgph.0006386.ref013","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.ajhg.2014.02.009","article-title":"Genetic origins of lactase persistence and the spread of pastoralism in Africa","volume":"94","author":"A Ranciaro","year":"2014","journal-title":"Am J Hum Genet"},{"key":"pgph.0006386.ref014","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1146\/annurev-genom-091416-035340","article-title":"On the Evolution of Lactase Persistence in Humans","volume":"18","author":"L S\u00e9gurel","year":"2017","journal-title":"Annu Rev Genomics Hum Genet"},{"issue":"2","key":"pgph.0006386.ref015","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/ng826","article-title":"Identification of a variant associated with adult-type hypolactasia","volume":"30","author":"NS Enattah","year":"2002","journal-title":"Nat Genet"},{"issue":"25","key":"pgph.0006386.ref016","doi-asserted-by":"crossref","first-page":"3508","DOI":"10.3748\/wjg.v13.i25.3508","article-title":"Correlation of intestinal disaccharidase activities with the C\/T-13910 variant and age","volume":"13","author":"N-S Enattah","year":"2007","journal-title":"World J Gastroenterol"},{"issue":"11","key":"pgph.0006386.ref017","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1136\/gut.2004.040048","article-title":"A genetic test which can be used to diagnose adult-type hypolactasia in children","volume":"53","author":"H Rasinper\u00e4","year":"2004","journal-title":"Gut"},{"key":"pgph.0006386.ref018","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1086\/421050","article-title":"The T allele of a single-nucleotide polymorphism 13.9 kb upstream of the lactase gene (LCT) (C-13.9kbT) does not predict or cause the lactase-persistence phenotype in Africans","volume":"74","author":"CA Mulcare","year":"2004","journal-title":"Am J Hum Genet"},{"issue":"1","key":"pgph.0006386.ref019","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.ajhg.2007.09.012","article-title":"Independent introduction of two lactase-persistence alleles into human populations reflects different history of adaptation to milk culture","volume":"82","author":"NS Enattah","year":"2008","journal-title":"Am J Hum Genet"},{"issue":"2","key":"pgph.0006386.ref020","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1097\/MPG.0000000000000595","article-title":"Functional significance of single nucleotide polymorphisms in the lactase gene in diverse US patients and evidence for a novel lactase persistence allele at -13909 in those of European ancestry","volume":"60","author":"NY Baffour-Awuah","year":"2015","journal-title":"J Pediatr Gastroenterol Nutr"},{"issue":"7","key":"pgph.0006386.ref021","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1007\/s00439-012-1140-z","article-title":"The human lactase persistence-associated SNP -13910*T enables in vivo functional persistence of lactase promoter-reporter transgene expression","volume":"131","author":"L Fang","year":"2012","journal-title":"Hum Genet"},{"issue":"9","key":"pgph.0006386.ref022","doi-asserted-by":"crossref","first-page":"7469","DOI":"10.3390\/nu7095348","article-title":"Additional Value of CH4 Measurement in a Combined 13C\/H2 Lactose Malabsorption Breath Test: A Retrospective Analysis","volume":"7","author":"E Houben","year":"2015","journal-title":"Nutrients"},{"key":"pgph.0006386.ref023","first-page":"1","article-title":"Methodology and indications of H2-breath testing in gastrointestinal diseases: the Rome Consensus Conference","author":"A Gasbarrini","year":"2009","journal-title":"Aliment Pharmacol Ther"},{"issue":"5","key":"pgph.0006386.ref024","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1038\/ajg.2017.46","article-title":"Hydrogen and Methane-Based Breath Testing in Gastrointestinal Disorders: The North American Consensus","volume":"112","author":"A Rezaie","year":"2017","journal-title":"Am J Gastroenterol"},{"key":"pgph.0006386.ref025","volume-title":"Molecular cloning: a laboratory manual","author":"J Sambrook","year":"1989","edition":"2"},{"issue":"5","key":"pgph.0006386.ref026","doi-asserted-by":"crossref","first-page":"460","DOI":"10.3109\/03014460.2013.877965","article-title":"An association between lactose intolerance and anthropometric variables in the Sudanese Shagia tribe (East Africa)","volume":"41","author":"A Kempi\u0144ska-Podhorodecka","year":"2014","journal-title":"Ann Hum Biol"},{"issue":"6","key":"pgph.0006386.ref027","first-page":"1127","article-title":"Evaluation of a genetic test for diagnose of primary hypolactasia in northeast of iran (khorasan)","volume":"15","author":"M Alizadeh","year":"2012","journal-title":"Iran J Basic Med Sci"},{"issue":"9","key":"pgph.0006386.ref028","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1016\/j.metabol.2013.04.006","article-title":"The lactase persistence genotype is associated with body mass index and dairy consumption in the D.E.S.I.R. study","volume":"62","author":"A Lamri","year":"2013","journal-title":"Metabolism"},{"issue":"1","key":"pgph.0006386.ref029","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.gene.2013.01.049","article-title":"Frequency of LCT-13910C\/T and LCT-22018G\/A single nucleotide polymorphisms associated with adult-type hypolactasia\/lactase persistence among Israelis of different ethnic groups","volume":"519","author":"M Raz","year":"2013","journal-title":"Gene"},{"issue":"3","key":"pgph.0006386.ref030","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1086\/520705","article-title":"Evidence of still-ongoing convergence evolution of the lactase persistence T-13910 alleles in humans","volume":"81","author":"NS Enattah","year":"2007","journal-title":"Am J Hum Genet"},{"issue":"8","key":"pgph.0006386.ref031","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0043978","article-title":"Association of the European lactase persistence variant (LCT-13910 C>T polymorphism) with obesity in the Canary Islands","volume":"7","author":"R Almon","year":"2012","journal-title":"PLoS One"},{"issue":"4","key":"pgph.0006386.ref032","doi-asserted-by":"crossref","DOI":"10.1111\/apa.12134","article-title":"The lactase persistence -13910C>T polymorphism shows indication of association with abdominal obesity among Portuguese children","volume":"102","author":"D Albuquerque","year":"2013","journal-title":"Acta Paediatr"},{"issue":"5","key":"pgph.0006386.ref033","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1007\/s12263-013-0335-9","article-title":"Associations of the lactase persistence allele and lactose intake with body composition among multiethnic children","volume":"8","author":"AJ Malek","year":"2013","journal-title":"Genes Nutr"},{"issue":"2","key":"pgph.0006386.ref034","doi-asserted-by":"crossref","first-page":"487","DOI":"10.3945\/ajcn.114.105049","article-title":"Milk intake is not associated with low risk of diabetes or overweight-obesity: a Mendelian randomization study in 97,811 Danish individuals","volume":"102","author":"HKM Bergholdt","year":"2015","journal-title":"Am J Clin Nutr"},{"issue":"1","key":"pgph.0006386.ref035","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1002\/ajpa.22313","article-title":"Brief communication: Effect of nomadic subsistence practices on lactase persistence associated genetic variation in Kuwait","volume":"152","author":"SC Hill","year":"2013","journal-title":"Am J Phys Anthropol"},{"issue":"10","key":"pgph.0006386.ref036","doi-asserted-by":"crossref","DOI":"10.1136\/jmg.2007.051631","article-title":"The T\/G 13915 variant upstream of the lactase gene (LCT) is the founder allele of lactase persistence in an urban Saudi population","volume":"44","author":"F Imtiaz","year":"2007","journal-title":"J Med Genet"},{"issue":"6","key":"pgph.0006386.ref037","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1007\/s00439-006-0291-1","article-title":"A novel polymorphism associated with lactose tolerance in Africa: multiple causes for lactase persistence?","volume":"120","author":"CJE Ingram","year":"2007","journal-title":"Hum Genet"},{"issue":"3","key":"pgph.0006386.ref038","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1353\/hub.2012.a486778","article-title":"Distribution of the lactase persistence-associated variant alleles -13910* T and -13915* G among the people of Oman and Yemen","volume":"84","author":"AR Al-Abri","year":"2012","journal-title":"Hum Biol"},{"issue":"5","key":"pgph.0006386.ref039","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1111\/ahg.12575","article-title":"The molecular basis of lactase persistence: Linking genetics and epigenetics","volume":"89","author":"CE Cohen","year":"2025","journal-title":"Ann Hum Genet"},{"issue":"5","key":"pgph.0006386.ref040","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1093\/oxfordjournals.aje.a115423","article-title":"Lactase persistence and milk consumption as determinants of ovarian cancer risk","volume":"130","author":"DW Cramer","year":"1989","journal-title":"Am J Epidemiol"},{"issue":"2","key":"pgph.0006386.ref041","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1093\/ajcn\/39.2.255","article-title":"Lactose maldigestion in Ascaris-infected preschool children","volume":"39","author":"E Carrera","year":"1984","journal-title":"Am J Clin Nutr"},{"issue":"6","key":"pgph.0006386.ref042","first-page":"637","article-title":"Milk consumption, galactose metabolism and ovarian cancer (Australia)","volume":"9","author":"PM Webb","year":"1998","journal-title":"Cancer Causes Control"},{"issue":"6","key":"pgph.0006386.ref043","first-page":"540","article-title":"Dietary lactose intake, lactose intolerance, and the risk of epithelial ovarian cancer in southern Ontario (Canada)","volume":"5","author":"HA Risch","year":"1994","journal-title":"Cancer Causes Control"},{"issue":"5","key":"pgph.0006386.ref044","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1093\/oxfordjournals.aje.a117443","article-title":"Lactose and galactose intake and metabolism in relation to the risk of epithelial ovarian cancer","volume":"141","author":"LJ Herrinton","year":"1995","journal-title":"Am J Epidemiol"}],"container-title":["PLOS Global Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgph.0006386","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T17:43:58Z","timestamp":1777916638000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgph.0006386"}},"subtitle":[],"editor":[{"given":"Mustafa A","family":"Barbhuiya","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2026,5,4]]},"references-count":44,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5,4]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pgph.0006386","relation":{},"ISSN":["2767-3375"],"issn-type":[{"value":"2767-3375","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,4]]}}}