The polymorphic expression of lactase in adults is regulated at the messenger RNA level

Fajardo, Osvaldo; Naim, Hassan Y.; Lacey, Stephen W.

doi:10.1016/0016-5085(94)90014-0

Cited by 44 publications

(18 citation statements)

References 17 publications

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“…Although previous studies have demonstrated a strong correlation between lactase enzyme levels and lactase mRNA expression (34, 39, 40), no threshold has been established for distinguishing lactase persistence from non-persistence using mRNA quantification. As shown for lactase enzyme activity, lactase mRNA levels increased from -13910C/C to -13910T/T ( P <0.001) (Figure 3a), with all three groups statistically different from one another ( P <0.05 for each).…”

Section: Resultsmentioning

confidence: 99%

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

Baffour-Awuah

Fleet

Montgomery

et al. 2015

J. pediatr. gastroenterol. nutr.

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Objectives Recent data from mainly homogeneous European and African populations implicate a 140 bp region 5′ to the transcriptional start site of LCT (the lactase gene) as a regulatory site for lactase persistence and non-persistence. As there are no studies of United States non-homogeneous populations, we performed genotype/phenotype analysis of the -13910 and -22018 LCT SNPs in New England children, mostly of European ancestry. Methods Duodenal biopsies were processed for disaccharidase activities, RNA quantification by RT-PCR, allelic expression ratios by PCR, and genotyping and SNP analysis. Results were compared to clinical information. Results Lactase activity and mRNA levels, as well as sucrase-to-lactase ratios of enzyme activity and mRNA, showed robust correlations with genotype. None of the other LCT SNPs showed as strong a correlation with enzyme or mRNA activities as did -13910. Data were consistent with the -13910 being the causal sequence variant rather than -22018. Four individuals heterozygous for -13910T/C had allelic expression patterns similar to individuals with -13910C/C genotypes; of these, 2 showed equal LCT expression from the 2 alleles and a novel variant (-13909C>A) associated with lactase persistence. Conclusion The identification of -13910C/C genotype is very likely to predict lactase non-persistence, consistent with prior published studies. A -13910T/T genotype will frequently, but not perfectly, predict lactase persistence in this mixed European-ancestry population; a -13910T/C genotype will not predict the phenotype. A long, rare haplotype in 2 individuals with -13910T/C genotype but equal allele-specific expression contains a novel lactase persistence allele present at -13909.

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Section: Resultsmentioning

confidence: 99%

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

Baffour-Awuah

Fleet

Montgomery

et al. 2015

J. pediatr. gastroenterol. nutr.

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“…Lactase persistence (LP) can be considered as a bypass of the transcriptional down-regulation of the LCT gene (Fajardo et al 1994) that normally occurs after weaning in lactase non-persistent (LNP) humans and other mammals Sebastio et al 1989;Torp et al 1993). The LP trait is believed to have evolved in populations where people have a long milk-drinking history.…”

Section: Introductionmentioning

confidence: 98%

The −14010*C variant associated with lactase persistence is located between an Oct-1 and HNF1α binding site and increases lactase promoter activity

et al. 2011

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In most people worldwide intestinal lactase expression declines in childhood. In many others, particularly in Europeans, lactase expression persists into adult life. The lactase persistence phenotype is in Europe associated with the -13910*T single nucleotide variant located 13,910 bp upstream the lactase gene in an enhancer region that affects lactase promoter activity. This variant falls in an Oct-1 binding site and shows greater Oct-1 binding than the ancestral variant and increases enhancer activity. Several other variants have been identified very close to the -13910 position, which are associated with lactase persistence in the Middle East and Africa. One of them, the -14010*C, is associated with lactase persistence in Africa. Here we show by deletion analysis that the -14010 position is located in a 144 bp region that reduces the enhancer activity. In transfections the -14010*C allele shows a stronger enhancer effect than the ancestral -4010*G allele. Binding sites for Oct-1 and HNF1α surrounding the -14010 position were identified by gel shift assays, which indicated that -14010*C has greater binding affinity to Oct-1 than -14010*G.

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“…These observations, in addition to findings of reduced lactase mRNA levels and reduced synthesis of the lactase precursor in the proximal small intestine (Lloyd, 1993;Auricchio and Maiuri, 1993;Rossi et a/. 1993;Ayuricchio, 1994;Fajardo et al, 1994), have led researchers to conclude that both pre-transcriptional as well as post-transcriptional control are involved in the regulation of lactase reduction in lactase-nonpersistent humans.…”

Section: (B) Lactase Regulation In Humansmentioning

confidence: 93%

Advanced Dairy Chemistry Volume 3

Fox¹

1997

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The polymorphic expression of lactase in adults is regulated at the messenger RNA level

Cited by 44 publications

References 17 publications

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

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

The −14010*C variant associated with lactase persistence is located between an Oct-1 and HNF1α binding site and increases lactase promoter activity

Advanced Dairy Chemistry Volume 3

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