{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T09:43:21Z","timestamp":1774086201836,"version":"3.50.1"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2019,2,21]],"date-time":"2019-02-21T00:00:00Z","timestamp":1550707200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Biol Rep"],"published-print":{"date-parts":[[2019,4]]},"DOI":"10.1007\/s11033-019-04696-9","type":"journal-article","created":{"date-parts":[[2019,2,21]],"date-time":"2019-02-21T11:19:18Z","timestamp":1550747958000},"page":"2379-2385","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Real-time PCR based detection of the lactase non-persistence associated genetic variant LCT-13910C>T directly from whole blood"],"prefix":"10.1007","volume":"46","author":[{"given":"Axel","family":"Muendlein","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Leiherer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Zach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva Maria","family":"Brandtner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Fraunberger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heinz","family":"Drexel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathrin","family":"Geiger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,2,21]]},"reference":[{"key":"4696_CR1","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1177\/2050640613484463","volume":"1","author":"B Misselwitz","year":"2013","unstructured":"Misselwitz B, Pohl D, Fr\u00fchauf H, Fried M, Vavricka SR, Fox M (2013) Lactose malabsorption and intolerance: pathogenesis, diagnosis and treatment. United Eur Gastroenterol J 1:151\u2013159","journal-title":"United Eur Gastroenterol J"},{"key":"4696_CR2","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1097\/MCG.0b013e3182889f0f","volume":"47","author":"M Levitt","year":"2013","unstructured":"Levitt M, Wilt T, Shaukat A (2013) Clinical implications of lactose malabsorption versus lactose intolerance. J Clin Gastroenterol 47:471\u2013480","journal-title":"J Clin Gastroenterol"},{"key":"4696_CR3","doi-asserted-by":"publisher","first-page":"1068","DOI":"10.1038\/ejcn.2016.80","volume":"70","author":"F Casellas","year":"2016","unstructured":"Casellas F, Aparici A, P\u00e9rez MJ, Rodr\u00edguez P (2016) Perception of lactose intolerance impairs health-related quality of life. Eur J Clin Nutr 70:1068\u20131072","journal-title":"Eur J Clin Nutr"},{"key":"4696_CR4","doi-asserted-by":"publisher","first-page":"2591","DOI":"10.1023\/A:1018841402133","volume":"42","author":"D Mishkin","year":"1997","unstructured":"Mishkin D, Sablauskas L, Yalovsky M, Mishkin S (1997) Fructose and sorbitol malabsorption in ambulatory patients with functional dyspepsia: comparison with lactose maldigestion\/malabsorption. Dig Dis Sci 42:2591\u20132598","journal-title":"Dig Dis Sci"},{"key":"4696_CR5","doi-asserted-by":"publisher","first-page":"2399","DOI":"10.1007\/s00198-018-4635-1","volume":"29","author":"Y Treister-Goltzman","year":"2018","unstructured":"Treister-Goltzman Y, Friger M, Peleg R (2018) Does primary lactase deficiency reduce bone mineral density in postmenopausal women? A systematic review and meta-analysis. Osteoporos Int 29:2399\u20132407","journal-title":"Osteoporos Int"},{"key":"4696_CR6","doi-asserted-by":"publisher","first-page":"174","DOI":"10.20524\/aog.2016.0009","volume":"29","author":"R Schiffner","year":"2016","unstructured":"Schiffner R, Kostev K, Gothe H (2016) Do patients with lactose intolerance exhibit more frequent comorbidities than patients without lactose intolerance? An analysis of routine data from German medical practices. Ann Gastroenterol 29:174\u2013179","journal-title":"Ann Gastroenterol"},{"key":"4696_CR7","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1146\/annurev.genet.37.110801.143820","volume":"37","author":"DM Swallow","year":"2003","unstructured":"Swallow DM (2003) Genetics of lactase persistence and lactose intolerance. Annu Rev Genet 37:197\u2013219","journal-title":"Annu Rev Genet"},{"key":"4696_CR8","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1016\/S0016-5085(98)70429-9","volume":"114","author":"Y Wang","year":"1998","unstructured":"Wang Y, Harvey CB, Hollox EJ, Phillips AD, Poulter M, Clay P et al (1998) The genetically programmed down-regulation of lactase in children. Gastroenterology 114:1230\u20131236","journal-title":"Gastroenterology"},{"key":"4696_CR9","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1086\/421051","volume":"74","author":"T Bersaglieri","year":"2004","unstructured":"Bersaglieri T, Sabeti PC, Patterson N, Vanderploeg T, Schaffner SF, Drake JA et al (2004) Genetic signatures of strong recent positive selection at the lactase gene. Am J Hum Genet 74:1111\u20131120","journal-title":"Am J Hum Genet"},{"key":"4696_CR10","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1038\/ng826","volume":"30","author":"NS Enattah","year":"2002","unstructured":"Enattah NS, Sahi T, Savilahti E, Terwilliger JD, Peltonen L, J\u00e4rvel\u00e4 I (2002) Identification of a variant associated with adult-type hypolactasia. Nat Genet 30:233\u2013237","journal-title":"Nat Genet"},{"key":"4696_CR11","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1046\/j.1469-1809.2003.00048.x","volume":"67","author":"M Poulter","year":"2003","unstructured":"Poulter M, Hollox E, Harvey CB, Mulcare C, Peuhkuri K, Kajander K et al (2003) The causal element for the lactase persistence\/non-persistence polymorphism is located in a 1 Mb region of linkage disequilibrium in Europeans. Ann Hum Genet 67:298\u2013311","journal-title":"Ann Hum Genet"},{"key":"4696_CR12","doi-asserted-by":"publisher","first-page":"2333","DOI":"10.1093\/hmg\/ddg244","volume":"12","author":"LC Olds","year":"2003","unstructured":"Olds LC, Sibley E (2003) Lactase persistence DNA variant enhances lactase promoter activity in vitro: functional role as a cis regulatory element. Hum Mol Genet 12:2333\u20132340","journal-title":"Hum Mol Genet"},{"key":"4696_CR13","doi-asserted-by":"publisher","first-page":"3945","DOI":"10.1093\/hmg\/ddi418","volume":"14","author":"RH Lewinsky","year":"2005","unstructured":"Lewinsky RH, Jensen TGK, M\u00f8ller J, Stensballe A, Olsen J, Troelsen JT (2005) T-13910 DNA variant associated with lactase persistence interacts with Oct-1 and stimulates lactase promoter activity in vitro. Hum Mol Genet 14:3945\u20133953","journal-title":"Hum Mol Genet"},{"key":"4696_CR14","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.1053\/j.gastro.2003.09.031","volume":"125","author":"JT Troelsen","year":"2003","unstructured":"Troelsen JT, Olsen J, M\u00f8ller J, Sj\u00f6str\u00f6m H (2003) An upstream polymorphism associated with lactase persistence has increased enhancer activity. Gastroenterology 125:1686\u20131694","journal-title":"Gastroenterology"},{"key":"4696_CR15","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1007\/s00439-012-1140-z","volume":"131","author":"L Fang","year":"2012","unstructured":"Fang L, Ahn JK, Wodziak D, Sibley E (2012) The human lactase persistence-associated SNP -13910*T enables in vivo functional persistence of lactase promoter-reporter transgene expression. Hum Genet 131:1153\u20131159","journal-title":"Hum Genet"},{"key":"4696_CR16","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1159\/000087050","volume":"71","author":"C B\u00fcning","year":"2005","unstructured":"B\u00fcning C, Genschel J, Jurga J, Fiedler T, Voderholzer W, Fiedler E-M et al (2005) Introducing genetic testing for adult-type hypolactasia. Digestion 71:245\u2013250","journal-title":"Digestion"},{"key":"4696_CR17","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1017\/S0007114510001297","volume":"104","author":"D Pohl","year":"2010","unstructured":"Pohl D, Savarino E, Hersberger M, Behlis Z, Stutz B, Goetze O et al (2010) Excellent agreement between genetic and hydrogen breath tests for lactase deficiency and the role of extended symptom assessment. Br J Nutr 104:900\u2013907","journal-title":"Br J Nutr"},{"key":"4696_CR18","first-page":"119","volume":"50","author":"BCM Haberkorn","year":"2011","unstructured":"Haberkorn BCM, Ermens AAM, Koeken A, Cobbaert CM, van Guldener C (2011) Improving diagnosis of adult-type hypolactasia in patients with abdominal complaints. Clin Chem Lab Med 50:119\u2013123","journal-title":"Clin Chem Lab Med"},{"key":"4696_CR19","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1086\/421050","volume":"74","author":"CA Mulcare","year":"2004","unstructured":"Mulcare CA, Weale ME, Jones AL, Connell B, Zeitlyn D, Tarekegn A et al (2004) 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. Am J Hum Genet 74:1102\u20131110","journal-title":"Am J Hum Genet"},{"key":"4696_CR20","first-page":"80","volume":"46","author":"TK Nilsson","year":"2008","unstructured":"Nilsson TK, Olsson LA (2008) Simultaneous genotyping of the three lactose tolerance-linked polymorphisms LCT -13907C>G, LCT -13910C>T and LCT -13915T>G with Pyrosequencing\u2122 technology. Clin Chem Lab Med 46:80\u201384","journal-title":"Clin Chem Lab Med"},{"key":"4696_CR21","doi-asserted-by":"publisher","first-page":"535","DOI":"10.3109\/00365513.2010.522251","volume":"70","author":"J Janukonyt\u00e9","year":"2010","unstructured":"Janukonyt\u00e9 J, Vestergaard EM, Ladefoged SA, Nissen PH (2010) High-resolution melting analysis using unlabeled probe and amplicon scanning simultaneously detects several lactase persistence variants. Scand J Clin Lab Invest 70:535\u2013540","journal-title":"Scand J Clin Lab Invest"},{"key":"4696_CR22","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1093\/ije\/dyv109","volume":"44","author":"HKM Bergholdt","year":"2015","unstructured":"Bergholdt HKM, Nordestgaard BG, Varbo A, Ellervik C (2015) Milk intake is not associated with ischaemic heart disease in observational or Mendelian randomization analyses in 98,529 Danish adults. Int J Epidemiol 44:587\u2013603","journal-title":"Int J Epidemiol"},{"key":"4696_CR23","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1373\/clinchem.2005.057240","volume":"52","author":"G Bodlaj","year":"2006","unstructured":"Bodlaj G, St\u00f6cher M, Hufnagl P, Hubmann R, Biesenbach G, Stekel H et al (2006) Genotyping of the lactase-phlorizin hydrolase\u201413910 polymorphism by LightCycler PCR and implications for the diagnosis of lactose intolerance. Clin Chem 52:148\u2013151","journal-title":"Clin Chem"},{"key":"4696_CR24","doi-asserted-by":"publisher","first-page":"1901","DOI":"10.1002\/ijc.27836","volume":"132","author":"RC Travis","year":"2013","unstructured":"Travis RC, Appleby PN, Siddiq A, Allen NE, Kaaks R, Canzian F et al (2013) Genetic variation in the lactase gene, dairy product intake and risk for prostate cancer in the European prospective investigation into cancer and nutrition. Int J Cancer 132:1901\u20131910","journal-title":"Int J Cancer"},{"key":"4696_CR25","doi-asserted-by":"publisher","first-page":"727","DOI":"10.7754\/Clin.Lab.2015.150923","volume":"62","author":"D Enko","year":"2016","unstructured":"Enko D, Pollheimer V, N\u00e9meth S, P\u00fchringer H, Stolba R, Halwachs-Baumann G et al (2016) Lactase non-persistence genotyping: comparison of two real-time PCR assays and assessment of concomitant fructose\/sorbitol malabsorption rates. Clin Lab 62:727\u2013730","journal-title":"Clin Lab"},{"key":"4696_CR26","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.cca.2018.03.029","volume":"482","author":"A Abildgaard","year":"2018","unstructured":"Abildgaard A, Tovbjerg SK, Giltay A, Detemmerman L, Nissen PH (2018) Lactase persistence genotyping on whole blood by loop-mediated isothermal amplification and melting curve analysis. Clin Chim Acta 482:50\u201356","journal-title":"Clin Chim Acta"},{"key":"4696_CR27","doi-asserted-by":"publisher","first-page":"2569","DOI":"10.1007\/s00216-018-0931-z","volume":"410","author":"M Sidstedt","year":"2018","unstructured":"Sidstedt M, Hedman J, Romsos EL, Waitara L, Wads\u00f6 L, Steffen CR et al (2018) Inhibition mechanisms of hemoglobin, immunoglobulin G, and whole blood in digital and real-time PCR. Anal Bioanal Chem 410:2569\u20132583","journal-title":"Anal Bioanal Chem"},{"key":"4696_CR28","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1590\/S0036-46652013000600005","volume":"55","author":"M Miura","year":"2013","unstructured":"Miura M, Tanigawa C, Fujii Y, Kaneko S (2013) Comparison of six commercially-available DNA polymerases for direct PCR. Rev Inst Med Trop Sao Paulo 55:401\u2013406","journal-title":"Rev Inst Med Trop Sao Paulo"},{"key":"4696_CR29","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/j.cca.2018.11.016","volume":"488","author":"K Geiger","year":"2019","unstructured":"Geiger K, Leiherer A, Brandtner E-M, Fraunberger P, Drexel H, Muendlein A (2019) Direct blood PCR: TaqMan-probe based detection of the venous thromboembolism associated mutations factor V Leiden and prothrombin c.20210G>A without DNA extraction. Clin Chim Acta 488:221\u2013225","journal-title":"Clin Chim Acta"},{"key":"4696_CR30","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/1471-2148-10-36","volume":"10","author":"Y Itan","year":"2010","unstructured":"Itan Y, Jones BL, Ingram CJE, Swallow DM, Thomas MG (2010) A worldwide correlation of lactase persistence phenotype and genotypes. BMC Evol Biol 10:36","journal-title":"BMC Evol Biol"},{"key":"4696_CR31","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1016\/S2468-1253(17)30154-1","volume":"2","author":"CL Storhaug","year":"2017","unstructured":"Storhaug CL, Fosse SK, Fadnes LT (2017) Country, regional, and global estimates for lactose malabsorption in adults: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2:738\u2013746","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"4696_CR32","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1086\/520705","volume":"81","author":"NS Enattah","year":"2007","unstructured":"Enattah NS, Trudeau A, Pimenoff V, Maiuri L, Auricchio S, Greco L et al (2007) Evidence of still-ongoing convergence evolution of the lactase persistence T-13910 alleles in humans. Am J Hum Genet 81:615\u2013625","journal-title":"Am J Hum Genet"},{"key":"4696_CR33","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.cca.2007.04.028","volume":"383","author":"M Kerber","year":"2007","unstructured":"Kerber M, Oberkanins C, Kriegsh\u00e4user G, Kollerits B, Dossenbach-Glaninger A, Fuchs D et al (2007) Hydrogen breath testing versus LCT genotyping for the diagnosis of lactose intolerance: A matter of age? Clin. Chim Acta 383:91\u201396","journal-title":"Chim Acta"},{"key":"4696_CR34","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1373\/clinchem.2004.031336","volume":"50","author":"A-N Spiess","year":"2004","unstructured":"Spiess A-N, Mueller N, Ivell R (2004) Trehalose is a potent PCR enhancer: lowering of DNA melting temperature and thermal stabilization of taq polymerase by the disaccharide trehalose. Clin Chem 50:1256\u20131259","journal-title":"Clin Chem"},{"key":"4696_CR35","doi-asserted-by":"publisher","first-page":"152","DOI":"10.2353\/jmoldx.2010.090070","volume":"12","author":"Z Zhang","year":"2010","unstructured":"Zhang Z, Kermekchiev MB, Barnes WM (2010) Direct DNA amplification from crude clinical samples using a PCR enhancer cocktail and novel mutants of Taq. J Mol Diagn 12:152\u2013161","journal-title":"J Mol Diagn"},{"key":"4696_CR36","doi-asserted-by":"crossref","first-page":"4463","DOI":"10.1128\/JCM.38.12.4463-4470.2000","volume":"38","author":"W Abu Al-Soud","year":"2000","unstructured":"Abu Al-Soud W, R\u00e5dstr\u00f6m P (2000) Effects of amplification facilitators on diagnostic PCR in the presence of blood, feces, and meat. J Clin Microbiol 38:4463\u20134470","journal-title":"J Clin Microbiol"},{"key":"4696_CR37","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1007\/s00439-006-0291-1","volume":"120","author":"CJE Ingram","year":"2007","unstructured":"Ingram CJE, Elamin MF, Mulcare CA, Weale ME, Tarekegn A, Raga TO et al (2007) A novel polymorphism associated with lactose tolerance in Africa: multiple causes for lactase persistence? Hum Genet 120:779\u2013788","journal-title":"Hum Genet"},{"key":"4696_CR38","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/ng1946","volume":"39","author":"SA Tishkoff","year":"2007","unstructured":"Tishkoff SA, Reed FA, Ranciaro A, Voight BF, Babbitt CC, Silverman JS et al (2007) Convergent adaptation of human lactase persistence in Africa and Europe. Nat Genet 39:31\u201340","journal-title":"Nat Genet"},{"key":"4696_CR39","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1093\/nar\/29.1.308","volume":"29","author":"ST Sherry","year":"2001","unstructured":"Sherry ST, Ward MH, Kholodov M, Baker J, Phan L, Smigielski EM et al (2001) dbSNP: the NCBI database of genetic variation. Nucleic Acids Res 29:308\u2013311","journal-title":"Nucleic Acids Res"}],"container-title":["Molecular Biology Reports"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s11033-019-04696-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11033-019-04696-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11033-019-04696-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,2,20]],"date-time":"2020-02-20T19:09:34Z","timestamp":1582225774000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s11033-019-04696-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,21]]},"references-count":39,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,4]]}},"alternative-id":["4696"],"URL":"https:\/\/doi.org\/10.1007\/s11033-019-04696-9","relation":{},"ISSN":["0301-4851","1573-4978"],"issn-type":[{"value":"0301-4851","type":"print"},{"value":"1573-4978","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,21]]},"assertion":[{"value":"17 December 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 February 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 February 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that they have no conflicts of interest related to the contents of this article.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All patients gave written confirmed consent for clinical LCT-13910C>T testing.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}