Academic literature on the topic 'Lactase gene (LCT)'

AbstractThe majority of mammals are unable to digest lactose due to post-weaning deactivation of the LCT gene, which is responsible for encoding the enzyme lactase (i.e., adult-type hypolactasia). A substitution of C with T at position −13910 bp upstream of the LCT gene has been linked to the lactase persistence phenotype in European populations. We investigated the frequency of LCT-13910C>T polymorphism in 223 blood donors from central Poland. All samples were genotyped by polymerase chain reaction and direct sequencing. The LCT-13910 T allele (lactase persistence) was present in 51% of individuals sampled from the Polish population. We did not find any non-European variants associated with lactase persistence (LCT-13907C>G, LCT-13913T>C, LCT-13915T>G), or any new polymorphisms within the sequenced region. Allele frequencies obtained are in agreement with results from other countries and confirm the unique pattern of distribution of the LCT-13910C>T genotype in Europe.

Lactose (β-galactosyl-1,4 glucose) is milk sugar, the main disaccharide of human and other mammalian breast milk. Lactase is intestinal disaccharidase that catalyzes the lactose hydrolysis. The lactase gene LCT controls biological function of the enzyme. The age-related genetically determined feature of disaccharide expression, epigenetic factors, and natural selection with persistent tolerance to milk sugar throughout lifetime has divided the human population according to the LCT gene into two phenotypes: lactase persistent and lactase non-persistent. There is conflicting evidence that the latter phenotype is associated with low calcium absorption and the development of osteoporosis. The regular use of fermented probiotic dairy products by individuals with the lactase non-persistence phenotype ensures the accumulation of peak bone mineralization and prevents osteoporosis.

To explore the mechanisms by which jejunal lactase activity is modified by carbohydrate and/or fat intake, mRNA levels and the absolute synthesis rate of lactase-phlorizin hydrolase (LPH) were determined in 6-wk-old rats that were fed either low-starch diets containing long-chain triacylglycerol (LCT, 73% energy as corn oil) or medium-chain triacylglycerol (MCT, 66% energy as MCT, 7% energy as corn oil), or a high-starch diet (70% energy as cornstarch) for 7 days. LPH mRNA levels in the jejunum were similar between LCT-fed and MCT-fed rats, but animals fed the high-starch diet exhibited a greater (2x) LPH mRNA level than other groups. The absolute synthesis rate of LPH, estimated by the flooding dose technique using [3H]phenylalanine, was greater (2.4x) in rats fed the high-starch diet than in other groups. A short-term force-feeding experiment revealed that sucrose was able to evoke LPH mRNA levels within 12 h but that a nonmetabolizable sugar (alpha-methylglucoside) was unable to enhance it. By contrast, animals fed the high-LCT diet showed a lower (by 30%) lactase activity than rats fed the low-starch, high-MCT diet, which was accompanied by not only a reduction of immunoreactive LPH in brush-border membranes but also a reduction in lactase activity per unit weight of immunoreactive LPH. These results suggest that both gene expression and posttranslational events of LPH might be influenced by dietary manipulations; carbohydrate intake primarily increases LPH mRNA levels, and LCT accelerates inactivation and/or degradation of lactase.

Introduction: Excess lactose in the diet of modern man causes the development of not only lactase deficiency, but it can be a factor that contributes to obesity. The aim: To study associations between obesity and genotype C/C 13910 of lactase gene (LCT) in children, to investigate the effectiveness of treatment using drug exogenous lactase and a low-lactose diet. Materials and methods: genotyping of lactase gene by real-time polymerase chain reaction, determining the level of lactose maldigestion by hydrogen breath test (HBT), estimating the insulin resistance with the HOMA-IR index in 70 obese children and 40 healthy children 6 - 18 years. Obese children with genotype C/C 13910 and lactose maldigestion (n=40) were randomized in two groups: children from group I (n=20) received an exogenous lactase preparation, and children from group II (n=20) - low-lactose diet. Results: in obese children, the genotype C/C 13910 is 2 times more often than in healthy children. Obese children with genotype C/C 13910 have a significantly higher value of HBT (32.8–39.8 ppm) compared to healthy children (p<0.05), and an increased value of the HOMA-IR index. After treatment, there was a significant decrease in HBT and the HOMA-IR index in the two comparison groups. Conclusions: signs of insulin resistance are observed in children with obesity, genotype C/C 13910 and lactose maldigestion. The use of exogenous lactase in the therapy or the administration of a low-lactose diet cause approximately the same decrease in the HOMA-IR index.

The C/T-13910 LCT is closely associated with lactase persistence and LCT has emerged as a new candidate gene for obesity, in particular in northern Europeans. The aim of this research is to investigate to what degree sex determines the association between the LCT variant and anthropometric traits in a cohort of healthy individuals. We recruited 1000 (500 males and 500 females aged 18–65 years) healthy blood donors. The C/T-13910 LCT polymorphism was genotyped using TaqMan assays. All individuals were phenotyped with respect to anthropometric characteristics. Prevalence of genotypes was 22.7% CC (lactase non-persistent, LNP), 58.6% CT, and 18.7% TT. LNP genotype was present less frequently among men p = .0005; OR 0.582 [0.425–0.794]. Therefore, in addition statistical calculations were performed separately for men and women. Additional analysis demonstrated an association between the CC genotypes and higher chest ( p = .03), waist ( p = .005), and forearm circumference ( p = .0004) or more lean body mass ( p = .04), than T-allele carriers in males. In females, they were not significantly different. Men consumed more milk ( p = .003), while women ate more yoghurt ( p = .001). Pearson’s correlation analysis showed that the higher intake of milk and dairy products was associated with higher fat body mass among men with lactase persistence. In Caucasian men, the LNP genotype is associated with reduced milk intake and dairy products, but more fat-free mass and higher forearm circumference, which may be relevant to dietary management for lactose intolerant.

Adult-type hypolactasia results from the progressive decline of lactase-phlorizin hydrolase activity in enterocytes after weaning. Lactase nonpersistence may determine a primary lactose intolerance with reduced diary product consumption, which is possibly related to an increased risk of colon cancer. Recently, a genetic variant C/T—13910 upstream of the lactase-phlorizin hydrolase ( LCT) gene has been strongly correlated with the lactase persistence/nonpersistence trait in both family and case-control studies. The authors validate a denaturing high-performance liquid chromatography (dHPLC)—based assay versus conventional genotype sequencing in detecting the C/T—13910 polymorphism of LCT and evaluate its prevalence in 2 different Italian geographical areas and in colorectal cancer patients. DNA samples of 157 healthy subjects and 124 colon cancer patients from Apulia and of 97 healthy subjects from Sardinia were evaluated for the C/T—13910 polymorphism by dHPLC, sequencing, and restriction fragment length polymorphism (RFLP). Under optimized conditions, dHPLC was as sensitive as DNA sequencing and detected a new genetic variant (T/C-13913) in 2 individuals that was not identified by RFLP assay. Frequency of lactase nonpersistence genotype (C/C—13910) was similar in healthy subjects from 2 different Italian geographical areas and not increased in patients with colorectal cancer. The results indicate that the dHPLC method may be used as a rapid, noninvasive, and laborsaving screening tool for genotyping C/T—13910 polymorphism, with high success, low cost, and reproducibility. ( Journal of Biomolecular Screening 2007:733-739)

Many patients with inflammatory bowel disease (IBD) restrict dairy products to control their symptoms. The aim of the study was to investigate the prevalence of lactose intolerance assessed with hydrogen breath test (H-BT) in IBD patients in clinical remission compared to a sex, age and BMI matched control population. We further detected the prevalence of three single nucleotide polymorphisms of the lactase (LCT) gene: the lactase non persistence LCT-13910 CC (wildtype) and the intermediate phenotype LCT-22018 CT and LCT-13910 AG; finally, we assess the correlation between genotype and H-BT. A total of 54 IBD patients and 69 control who underwent clinical evaluation, H-BT and genetic test were enrolled. H-BT was positive in 64.8% IBD patients and 62.3% control (p = 0.3). The wild-type genotype was found in 85.2% IBD patients while CT-22018, AG-13910 and CT-22018/AG-13910 polymorphisms were found in 9.3%, 1.8% and 3.7%. In the control group, the wild-type genotype, CT-22018, AG-13910 and CT-22018/AG-13910 polymorphisms were found in 87%, 5.8%, 5.8% and 1.4% of cases, respectively. Therefore, the wild-type and polymorphisms’ prevalence did not differ between IBD population and control group (85.2% vs. 87%, p = 0.1) (14.8% vs. 13%, p = 0.7). The correlation between positive H-BT and genetic analysis showed that the wild-type genotype was associated with higher rate of lactose intolerance in the total population (OR 5.31, 95%CI 1.73–16.29, p = 0.003) and in the IBD (OR 7.61, 95%CI 1.36–42.7, p = 0.02). The prevalence of lactose intolerance in IBD patients did not differ from that of control. Despite suggestive symptoms, about 1/3 of IBD patients are not lactose intolerant, thus not needing “a priori” elimination diet. This may encourage a rationale and balanced dietary management in IBD.

A hipolactasia do tipo adulto é o fenótipo determinado pela diminuição da expressão da lactase após o período de lactação. Ela ocorre em um grande número de adultos em todo o mundo. A lactase é produzida pelos enterócitos e sua função principal é hidrolisar a lactose, que é o carboidrato do leite. Os indivíduos intolerantes à lactose irão apresentar sintomas como inchaço, flatulência, náusea e diarreia causados pela fermentação da lactose. A persistência da lactase (PL) é o fenótipo no qual a expressão da lactase se mantém elevada durante toda a vida. Na Europa, a PL foi relacionada a um polimorfismo de base única (SNP) localizado a aproximadamente 14 Kb do sítio de início da transcrição do LCT (gene da lactase), dentro de um íntron do gene MCM6, sendo este SNP uma troca de C para T na posição -13910 (rs4988235). Na África e Oriente Médio os seguintes SNPs foram relacionados a PL: - 13907C>G (rs41525747), -13915T>G (rs41380347), -14010G>C (rs145946881). O gene LCT também possui SNPs na região codificadora e na região promotora que não estão envolvidos com a PL. Estes SNPs apresentam alto desequilíbrio de ligação formando haplótipos, sendo que os haplótipos A, B, C e U são os mais frequentes na maioria das populações. No Brasil, dados sobre os alelos relacionados com a persistência da lactase são escassos. Além disso, dados populacionais relacionados à diversidade do gene LCT ainda não foram descritos para nossas populações. Portanto, o objetivo deste trabalho foi estudar a diversidade do gene LCT, da região codificadora do gene, da região promotora proximal e da região enhancer população brasileira. Um total de 1297 indivíduos foram analisados. As populações estudadas foram nativos brasileiros (Kaingang N=72, Xavante N=101, Guarani-Kaiowá N=84 e Guarani-Ñandeva N=59), eurodescendentes de Porto Alegre (Rio Grande do Sul, N=337), afrodescendentes de Porto Alegre (N=182), miscigenados de Belém (Pará, N=200) e de Recife (Pernambuco, N=262). Doze SNPs foram analisados, 10 nas regiões codificadora e promotora do LCT e 2 na região enhancer. As metodologias utilizadas na genotipagem destes SNPs foram PCR-RFLP, discriminação alélica pelo sistema TaqMan e sequenciamento. O sequenciamento também foi utilizado na busca de novos alelos da região enhancer. Com relação à população nativa, o único alelo de PL encontrado foi o -13910*T, variando de 0,5% em Xavante a 7,6% nos GuaraniÑandeva. O gene LCT foi altamente polimórfico apresentando 15 haplótipos com distribuição heterogênea nas populações nativas. Na população brasileira em geral, a frequência do alelo -13910*T foi maior (0,295) nos eurodescendentes de Porto Alegre e menor (0,175) na população de Belém. Nos grupos de afrodescendentes de Porto Alegre, Belém e Recife, 4 outras variantes, previamente descritas, da região enhancer foram encontradas: - 13779G>C, -13937G>A, -14010G>C, -14011C>T. Vinte e seis haplótipos previamente descritos foram identificados. O estudo de associação da presença do alelo -13910*T com a presença da síndrome metabólica nos eurodescendentes de Porto Alegre demonstrou que os indivíduos persistentes apresentam menor risco do que os não persistente de ter síndrome metabólica (OR=0,47; p=0,023). Na tentativa de auxiliar no entendimento das causas da PL foi realizado um estudo funcional da variante -13937G>A. Os resultados demonstraram que o alelo derivado não direciona maior expressão do gene repórter em células em cultura. Considerando os dados obtidos no presente trabalho e os disponíveis na literatura, ressaltamos a importância dos estudos que buscam compreender a PL pela busca de novos alelos, por estudos de correlação fenótipo-genótipo e também pelos estudos funcionais para a caracterização das variantes encontradas em relação ao fenótipo da lactase.
Adult-type hypolactasia is the phenotype determined by the decreased lactase expression after weaning. It occurs in a high number of adults in the world. Lactase is produced by the enterocytes and its major function is to hydrolyze lactose, the milk carbohydrate. The lactose intolerant individuals will have symptoms like bloating, flatulence, nausea and diarrhea caused by the lactose fermentation. Lactase persistence (LP) is the high lactase expression during adulthood. In Europe, the LP was related to a single nucleotide polymorphism (SNP) located approximately 14 Kb from the LCT (lactase gene) transcription initiation site, within a MCM6 gene intron, and this SNP is a C to T mutation in the -13910 position (rs4988235). In Africa and Middle East, the following SNPs were related to LP: - 13907C>G (rs41525747), -13915T>G (rs41380347), -14010G>C (rs145946881). LCT gene also has SNPs in the coding and promoter region that are not involved in the LP. These SNPs have high linkage disequilibrium forming haplotypes, with the A, B, C and U being the most frequent haplotypes in the majority of the populations. In Brazil, data about the LP related alleles are rare. Moreover, population data related to LCT gene diversity was not described for our population. Hence, the aim of this work was to study the LCT gene diversity in the coding region, in the proximal promoter region, and in the enhancer region in the Brazilian population. In total, 1297 individuals were investigated. The populations studied were Brazilian natives (Kaingang N=72, Xavante N=101, Guarani-Kaiowá N=84 and Guarani-Ñandeva N=59), Eurodescendants from Porto Alegre (Rio Grande do Sul state N=337), Afrodescendants from Porto Alegre (N=182), admixed individuals from Belém (Pará state, N=200) and from Recife (Pernambuco state, N=262). We analyzed 12 SNPs, 10 in the coding and promoter region of the LCT gene and 2 in the enhancer region. The genotyping methodologies applied were PCRRFLP, allelic discrimination by TaqMan system and sequencing. Sequencing was also employed for new alleles identification in the enhancer region. In relation to the native population, the only LP allele found was -13910*T, and the frequency ranged from 0.5% in Xavante to 7.6% in Guarani-Ñandeva. The LCT gene was highly polymorphic showing 15 haplotypes with heterogeneous distribution in the native populations. In the general population, the frequency of the -13910*T was higher (0.295) in Eurodescendants from Porto Alegre and lower (0.175) in the Belém population. In the groups of Afrodescendants from Porto Alegre, Belém and Recife, 4 other previously described variants in the enhancer region were found: -13779G>C, - 13937G>A, -14010G>C, -14011C>T. Twenty-six haplotypes previously described were found in the Brazilian population. The association study of the -13910*T allele and of the presence of the metabolic syndrome in the Eurodescendants from Porto Alegre showed that the persistent individuals have lower risk than the non-persistent of developing metabolic syndrome (OR=0.47, p=0.023). In an attempt to disclose LP causality, a functional study of the -13937G>A variant was performed. The results showed that the derived allele does not drive a higher expression of the reporter gene in cells in culture. Considering the results of this study and the data available in the literature, we emphasize the importance of the studies that try to determine the LP looking for new alleles, phenotype-genotype studies, and functional studies to characterize the variants found related to the lactase phenotype.