EVALUATION OF AGREEMENT BETWEEN C/T-13910 POLYMORPHISM GENOTYPING RESULTS AND LACTOSE TOLERANCE TEST RESULTS: A RETROSPECTIVE POPULATION-BASED STUDY IN BRAZIL.

BACKGROUND: Lactose tolerant test (LTT) is the most broadly used diagnostic test for lactose intolerance in Brazil, is an indirect, minimally invasive and a low-cost test that is widely available in primary care and useful in clinical practice. The C/T-13910 polymorphism in lactase persistence has been well characterized in Caucasian populations, but there are no studies evaluating the concordance between C/T-13910 polymorphism genotyping results and LTT results in Brazil, where the population is highly mixed. OBJECTIVE: We aimed to evaluate agreement between presence of C/T-13910 polymorphism genotyping and malabsorption in LTT results. METHODS: This is a retrospective analysis of a Brazilian population whose data were collected from a single laboratory database present in several Brazilian states. Results of individuals who underwent both genetic testing for lactose intolerance (C/T-13910 polymorphism genotyping) and an LTT from April 2016 until February 2019 were analysed to evaluate agreement between tests. Groups were classified according to age (<10-year-old (yo), 10-17 yo, ≥18 yo groups) and state of residence (São Paulo or Rio Grande do Sul). Results: Among the 404 patients evaluated, there was agreement between the genotyping and LTT results in 325 (80.4%) patients and discordance in 79 (19.6%) patients (k=0.42 -moderate agreement). Regarding the genotype, 47 patients with genotype C/C (lactase nonpersistence) had normal LTT results, and 32 with genotype C/T or T/T (indicating lactase persistence) had abnormal LTT results. Neither age nor state of residence (Rio Grande do Sul or São Paulo) affected the agreement between test results. CONCLUSION: Considering the moderate agreement between C/T-13910 polymorphism genotyping and LTT results (κ=0.42) in the Brazilian population, we hypothesize that an analysis of other polymorphisms could be a strategy to improve the agreement between genotyping and established tests and suggest that additional studies should focus on exploring this approach. BACKGROUND: • Lactose intolerance is highly prevalent and may be implicated as a cofactor, or as a differential diagnosis, in many gastrointestinal conditions. BACKGROUND: • The C/T-13910 polymorphism in lactase persistence is well characterized in Caucasian populations for lactase persistence. BACKGROUND: • Concordance between genotyping and functional tests does not occur in all patients. BACKGROUND: • Brazil has a highly mixed population and knowledge regarding presence of other polymorphisms is of importance in clarifying difficult cases.

Genetic and Oral Tests for the Diagnosis of Lactose Intolerance in Mixed-Ancestry Brazilians with Metabolic Syndrome.

BACKGROUND/AIMS: Metabolic syndrome (MetS) comprises a cluster of physiological and anthropometric abnormalities. MetS has been linked to lactose intolerance (LI). The aim of this study was to compare the sensitivity and specificity to detect LI using 2 different tests: (1) a genetic test and (2) an oral lactose tolerance test (OLTT). METHODS: Two hundred and fifty-four MetS patients, ≥20 years of age, of both genders, were recruited for this comparative study. Nine single nucleotide polymorphisms (SNPs) were selected for genetic investigation: rs182549and rs4988235(both considered "gold standard"); rs56064699; rs148142676; rs562211644; rs59533246; rs3754689; rs2278544,and rs10552864(as potential novel SNPs). Sensitivity and specificity, as well as positive and negative predictive values, were calculated for each genotype using WINPEPI version 11.65. Differences between positive and negative OLTT groups were considered statistically significant when p ≤ 0.05. RESULTS: Among the selected SNPs, only rs182549(p < 0.001) and rs4988235(p < 0.001) gave similar results compared to an OLTT. The sensitivity of both SNPs to detect LI was 87 and 86%, and specificity was 83 and 82.5%, respectively. CONCLUSION: Genetic tests using rs182549and rs4988235SNPs showed high agreement with OLTT. These genetic tests may be a good option to replace OLTT in MetS patients.

Prevalence of lactose intolerance in Chile: a double-blind placebo study.

BACKGROUND AND STUDY AIMS: Lactase non-persistence (LNP), or primary hypolactasia, is a genetic condition that mediates lactose malabsorption and can cause lactose intolerance. Here we report the prevalence of lactose intolerance in a double-blind placebo study. METHODS: The LCT C>T-13910 variant was genotyped by RT-PCR in 121 volunteers and lactose malabsorption was assessed using the hydrogen breath test (HBT) after consuming 25 g of lactose. Lactose intolerance was assessed by scoring symptoms (SS) using a standardized questionnaire following challenge with a lactose solution or saccharose placebo. RESULTS: The LNP genotype was observed in 57% of the volunteers, among whom 87% were HBT⁺. In the HBT⁺ group the median SS was 9 and in the HBT⁻ group the median SS was 3 (p < 0.001). No difference was observed in the SS when both groups were challenged with the placebo. The most common symptoms included audible bowel sounds, abdominal pain and meteorism. In the ROC curve analysis, an SS ≥ 6 demonstrated 72% sensitivity and 81% specificity for predicting a positive HBT. To estimate prevalence, lactose intolerance was defined as the presence of an SS ≥ 6 points after subtracting the placebo effect and 34% of the study population met this definition. CONCLUSIONS: The LNP genotype was present in more than half of subjects evaluated and the observed prevalence of lactose intolerance was 34%.

Comparison of Quick Lactose Intolerance Test in duodenal biopsies of dyspeptic patients with single nucleotide polymorphism LCT-13910C>T associated with primary hypolactasia/lactase-persistence.

PURPOSE: To analyze the usefulness of Quick Lactose Intolerance Test in relation to the genetic test based on LCT-13910C>T genotypes, previously validated for clinical practice, for primary hypolactasia/lactase-persistence diagnosis. METHODS: Thirty-two dyspeptic patients that underwent upper gastrointestinal endoscopy entered the study. Two postbulbar duodenal biopsies were taken for the Quick test, and gastric antral biopsy for DNA extraction and LCT-13910C>T polymorphism analysis. DNA was also extracted from biopsies after being used in the Quick Test that was kept frozen until extraction. RESULTS: Nine patients with lactase-persistence genotype (LCT-13910CT or LCT-13910TT) had normolactasia, eleven patients with hypolactasia genotype (LCT-13910CC) had severe hypolactasia, and among twelve with mild hypolactasia, except for one that had LCT-13910CT genotype, all the others had hypolactasia genotype. The agreement between genetic test and quick test was high (p<0.0001; Kappa Index 0.92). Most of the patients that reported symptoms with lactose-containing food ingestion had severe hypolactasia (p<0.05). Amplification with good quality PCR product was also obtained with DNA extracted from biopsies previously used in the Quick Test; thus, for the future studies antral gastric biopsies for genetic test would be unnecessary. CONCLUSION: Quick test is highly sensitive and specific for hypolactasia diagnosis and indicated those patients with symptoms of lactose intolerance.

Comparison of Quick Lactose Intolerance Test in duodenal biopsies of dyspeptic patients with single nucleotide polymorphism LCT-13910C>T associated with primary hypolactasia/lactase-persistence / Comparação do Teste Quick de Intolerância à Lactose em biópsias duodenais de pacientes dispépticos com polimorfismo de nucleotídeo único LCT-13910C>T associado com hipolactasia primária/lactase persistente

PURPOSE: To analyze the usefulness of Quick Lactose Intolerance Test in relation to the genetic test based on LCT-13910C>T genotypes, previously validated for clinical practice, for primary hypolactasia/lactase-persistence diagnosis. METHODS: Thirty-two dyspeptic patients that underwent upper gastrointestinal endoscopy entered the study. Two postbulbar duodenal biopsies were taken for the Quick test, and gastric antral biopsy for DNA extraction and LCT-13910C>T polymorphism analysis. DNA was also extracted from biopsies after being used in the Quick Test that was kept frozen until extraction. RESULTS: Nine patients with lactase-persistence genotype (LCT-13910CT or LCT-13910TT) had normolactasia, eleven patients with hypolactasia genotype (LCT-13910CC) had severe hypolactasia, and among twelve with mild hypolactasia, except for one that had LCT-13910CT genotype, all the others had hypolactasia genotype. The agreement between genetic test and quick test was high (p<0.0001; Kappa Index 0.92). Most of the patients that reported symptoms with lactose-containing food ingestion had severe hypolactasia (p<0.05). Amplification with good quality PCR product was also obtained with DNA extracted from biopsies previously used in the Quick Test; thus, for the future studies antral gastric biopsies for genetic test would be unnecessary. CONCLUSION: Quick test is highly sensitive and specific for hypolactasia diagnosis and indicated those patients with symptoms of lactose intolerance.

OBJETIVO: Analisar a aplicabilidade do Teste Quick de Intolerância à Lactose em relação ao teste genético baseado nos genótipos LCT-13910C>T, previamente validado para a prática clínica, para diagnóstico de má digestão primária de lactose/digestão de lactose. MÉTODOS: Trinta e dois pacientes dispépticos submetidos à endoscopia digestiva entraram no estudo. Duas biópsias duodenais pós-bulbares foram empregadas no Teste Quick, e biópsia do antro gástrico para extração de DNA e análise do polimorfismo LCT-13910C>T. DNA também foi extraído de biópsias depois de terem sido usadas no teste Quick, e conservadas congeladas. RESULTADOS: Nove pacientes com genótipo de lactase persistente (LCT-13910CT ou LCT-13910TT) tinham normolactasia, onze pacientes com genótipo de hipolactasia (LCT-13910CC) tinham hipolactasia severa, e entre doze com hipolactasia leve, com exceção de uma que tinha genótipo LCT-13910CT, todos os demais tinham genótipo de hipolactasia. A concordância entre o teste genético e o Quick Teste foi alta (p<0,0001; Índice Kappa=0,92). A maioria dos pacientes que relataram sintomas com ingestão de alimentos com lactose tinham hipolactasia severa (p<0,05). Amplificação com produto de PCR foi obtido com DNA extraído das biópsias usadas no teste Quick; portanto, nos trabalhos futuros seria desnecessário coletar biópsia do antro gástrico para o teste genético. CONCLUSÃO: O Teste Quick é altamente sensível e específico para diagnóstico de hipolactasia e indicou aqueles pacientes com sintomas de intolerância à lactose.

Diagnóstico de intolerancia a la lactosa en adultos: rendimiento comparativo de la clínica, test de hidrógeno espirado y test genético / Comparative performance of symptoms questionnaire, hydrogen test and genetic test for lactose intolerance

Background: Genetically programmed adult-type hypolactasia affects 56% of Chilean population. Ideally, diagnosis should be confirmed. Aim: To compare diagnostic yield of genetic test, hydrogen (H2) expiratory test and a validated symptomatic structured survey (SS). Material and Methods: Patients submitted to H2 test answered a historic (anamnestic) and current SS (after the ingestion of 25 g of lactose). A blood sample was obtained for determination of genetic polymorphisms C/T_13910, C/G_13907 and G/A_22018 by polymerase chain reaction. The gold standard for diagnosis of lactose intolerance (LI) was the agreement of at least two of three tests. Results: Sixty-one participants aged 39 ± 12 years (21 males), were studied. Anamnestic SS was diagnostic of LI in all cases (score > 7), while current SS detected LI in 27/61 (46%). H2 test (an increase > 15 ppm after ingestion of 25 g of lactose) showed LI in 31/61 (51%). The locus C/G_13907 showed no polymorphism and locus G/A_22018 was in complete linkage disequilibrium with C/T_13910. Genotype C/C_13910, associated to hypolactasia, was present in 30/58 (52%). According to the gold-standard, 32/61 (52.5%) patients were diagnosed as LI. Sensitivity and specificity were, respectively, 79% and 69% for current SS, 93% and 93% for H2 test and 97% and 93% for the genetic test. The last two showed a positive likelihood ratio (LR) > 10 and a negative LR < 0.1, figures within the range considered clinically useful. Conclusions: Genotype C/C_13910 is responsible for hypolactasia in this population. Anamnestic report of symptoms after milk ingestion and symptoms after lactose ingestion, are not accurate enough. H2 and genetic tests are simple and similarly accurate to diagnose lactose intolerance in adults.

Diagnosis of adult-type hypolactasia/lactase persistence: genotyping of single nucleotide polymorphism (SNP C/T-13910) is not consistent with breath test in Colombian Caribbean population.

CONTEXT: Genotyping of single nucleotide polymorphism (SNP C/T(-13910)) located upstream of the lactase gene is used to determine adult-type hypolactasia/lactase persistence in North-European Caucasian subjects. The applicability of this polymorphism has been studied by comparing it with the standard diagnostic methods in different populations. OBJECTIVE: To compare the lactose hydrogen breath test with the genetic test in a sample of the Colombian Caribbean population. METHODS: Lactose hydrogen breath test and genotyping of SNP C/T(-13910) were applied to 128 healthy individuals (mean age 35 ± 1). A positive lactose hydrogen breath test was indicative of hypolactasia. Genotyping was done using polymerase chain reaction/restriction fragment length polymorphism. The kappa index was used to establish agreement between the two methods. RESULTS: Seventy-six subjects (59%) were lactose-maldigesters (hypolactasia) and 52 subjects (41%) were lactose-digesters (lactase persistence). The frequencies of the CC, CT and TT genotypes were 80%, 20% and 0%, respectively. Genotyping had 97% sensitivity and 46% specificity. The kappa index = 0.473 indicates moderate agreement between the genotyping of SNP C/T(-13910) and the lactose hydrogen breath test. CONCLUSION: The moderate agreement indicates that the genotyping of the SNP C/T(-13910) is not applicable to determine adult-type hypolactasia/lactase persistence in the population participating in this study.

Diagnosis of adult-type hypolactasia/lactase persistence: genotyping of single nucleotide polymorphism (SNP C/T-13910) is not consistent with breath test in Colombian Caribbean population / Diagnóstico de hipolactasia tipo adulto/persistência da lactase: a genotipagem do polimorfismo de um único nucleotídeo (SNP) C/T-13910 não é consistente com o teste de hidrogênio na população do Caribe Colombiano

CONTEXT: Genotyping of single nucleotide polymorphism (SNP C/T-13910) located upstream of the lactase gene is used to determine adult-type hypolactasia/lactase persistence in North-European Caucasian subjects. The applicability of this polymorphism has been studied by comparing it with the standard diagnostic methods in different populations. OBJECTIVE: To compare the lactose hydrogen breath test with the genetic test in a sample of the Colombian Caribbean population. METHODS: Lactose hydrogen breath test and genotyping of SNP C/T-13910 were applied to 128 healthy individuals (mean age 35 ± 1). A positive lactose hydrogen breath test was indicative of hypolactasia. Genotyping was done using polymerase chain reaction/restriction fragment length polymorphism. The kappa index was used to establish agreement between the two methods. RESULTS: Seventy-six subjects (59%) were lactose-maldigesters (hypolactasia) and 52 subjects (41%) were lactose-digesters (lactase persistence). The frequencies of the CC, CT and TT genotypes were 80%, 20% and 0%, respectively. Genotyping had 97% sensitivity and 46% specificity. The kappa index = 0.473 indicates moderate agreement between the genotyping of SNP C/T-13910 and the lactose hydrogen breath test. CONCLUSION: The moderate agreement indicates that the genotyping of the SNP C/T-13910 is not applicable to determine adult-type hypolactasia/lactase persistence in the population participating in this study.

CONTEXTO: A genotipagem do SNP C/T-13910 localizado corrente acima do gene da lactase é usada para determinar hipolactasia e persistência da lactase tipo adulto em indivíduos caucasianos do Norte da Europa. A aplicabilidade deste polimorfismo tem sido estudada em comparação com métodos padronizados de diagnóstico em diferentes populações. OBJETIVO: Comparar o teste de hidrogênio expirado após a ingestão de lactose com o teste genético em uma mostra da população do Caribe Colombiano. MÉTODOS: O teste de hidrogênio expirado após a ingestão de lactose e a genotipagem do SNP C/T-13910 foram aplicados em 128 sujeitos sadios (idade media 35 ± 1). O teste de hidrogênio positivo foi indicativo de hipolactasia. A genotipagem foi feita pelo método "polymerase chain reaction/restriction fragment length polymorphism". O índice Kappa foi utilizado para estabelecer a concordância entre os dois métodos. RESULTADOS: Setenta e seis indivíduos (59%) foram mau digestores da lactose (hipolactasia) e 52 outros (41%) foram digestores da lactose (persistência da lactase). As frequências dos genotipos CC, CT e TT foram 80%, 20% e 0%, respectivamente. A genotipagem mostrou 97% da sensibilidade e 46% da especificidade. O índice kappa: 0,473 indicou moderada concordância entre os dois métodos. CONCLUSÃO: A moderada concordância indica que a genotipagem do SNP C/T-13910 nao é aplicável para determinar hipolactasia tipo adulto/persistência da lactase na população estudada.

[Comparative performance of symptoms questionnaire, hydrogen test and genetic test for lactose intolerance]. / Diagnóstico de intolerancia a la lactosa en adultos: rendimiento comparativo de la clínica, test de hidrógeno espirado y test genético.

BACKGROUND: Genetically programmed adult-type hypolactasia affects 56% of Chilean population. Ideally, diagnosis should be confirmed. AIM: To compare diagnostic yield of genetic test, hydrogen (H2) expiratory test and a validated symptomatic structured survey (SS). MATERIAL AND METHODS: Patients submitted to H2 test answered a historic (anamnestic) and current SS (after the ingestion of 25 g of lactose). A blood sample was obtained for determination of genetic polymorphisms C/T_13910, C/G_13907 and G/A_22018 by polymerase chain reaction. The gold standard for diagnosis of lactose intolerance (LI) was the agreement of at least two of three tests. RESULTS: Sixty-one participants aged 39 ± 12 years (21 males), were studied. Anamnestic SS was diagnostic of LI in all cases (score > 7), while current SS detected LI in 27/61 (46%). H2 test (an increase > 15 ppm after ingestion of 25 g of lactose) showed LI in 31/61 (51%). The locus C/G_13907 showed no polymorphism and locus G/A_22018 was in complete linkage disequilibrium with C/T_13910. Genotype C/C_13910, associated to hypolactasia, was present in 30/58 (52%). According to the gold-standard, 32/61 (52.5%) patients were diagnosed as LI. Sensitivity and specificity were, respectively, 79% and 69% for current SS, 93% and 93% for H2 test and 97% and 93% for the genetic test. The last two showed a positive likelihood ratio (LR) > 10 and a negative LR < 0.1, figures within the range considered clinically useful. CONCLUSIONS: Genotype C/C_13910 is responsible for hypolactasia in this population. Anamnestic report of symptoms after milk ingestion and symptoms after lactose ingestion, are not accurate enough. H2 and genetic tests are simple and similarly accurate to diagnose lactose intolerance in adults.

Intolerancia a la lactosa / Lactose intolerance

La lactosa es un disacárido de amplia distribución en la dieta y productos farmacéuticos, es el hidrato de carbono de la leche de los mamíferos. La intolerancia a la lactosa puede presentarse como congénita, hipolactasia del desarrollo, primaria y secundaria. Frente a la sospecha de ésta patología la clínica es lo principal, pudiendo investigarla a través de la prueba contraprueba, la prueba de hidrógeno espirado, la biopsia y por estudio de polimorfismos a través biología molecular (aún en estudio). Su tratamiento consiste en la disminución o exclusión de lactosa, uso de suplementos lácteos, sin olvidar la ingesta mínima requerida de calcio y vitamina D importantes en el desarrollo óseo.

[Lactose intolerance: changing paradigms due to molecular biology]. / Intolerância à lactose: mudança de paradigmas com a biologia molecular.

In most mammals, lactase activity declines on the intestinal wall after weaning, characterizing primary hypolactasia that provokes symptoms of lactose intolerance. The intensity of symptoms of distention, flatulence, abdominal pain and diarrhea varies, according to the amount of ingested lactose, and increases with age. Hypolactasia is genetically determined; nonetheless, a mutation occurred that had made a part of mankind tolerate milk in adulthood. Diagnosis is made by a tolerance test, using the lactose challenge. With the discovery made by the Finns of polymorphism associated with lactase persistence, mainly, in Northern Europe, the genetic test was incorporated as a more comfortable diagnostic tool for the intolerant. In Brazil, 43% of Caucasian and Mulatto groups have lactase persistence allele, with hipolactasia more frequently found among Blacks and Japanese. However, in clinical practice people with hypolactasia may be advised to consume certain dairy products and food containing lactose without developing intolerance symptoms, whereas others will need a lactose restriction diet.

Intolerância à lactose: mudança de paradigmas com a biologia molecular / Lactose intolerance: changing paradigms due to molecular biology

Na maioria dos mamíferos a atividade da enzima lactase diminui na parede intestinal após o desmame, caracterizando a hipolactasia primária que provoca sintomas de intolerância à lactose. A intensidade dos sintomas de distensão, flatulência, dor abdominal e diarreia variam, dependendo da quantidade de lactose ingerida, e aumentam com o passar da idade. A hipolactasia é determinada geneticamente, porém uma mutação ocorreu para que fizesse parte da humanidade tolerar o leite na idade adulta. O diagnóstico é feito por teste de tolerância, empregando a lactose como desafio. Com a descoberta dos finlandeses do polimorfismo associado com a persistência da lactase, principalmente no norte da Europa, o exame genético passou a ser outra ferramenta diagnóstica mais confortável para o intolerante. No Brasil, 43 por cento dos brancos e dos mulatos têm alelo de persistência da lactase, sendo a hipolactasia mais frequente entre os negros e japoneses. Entretanto, na prática clínica indivíduos com hipolactasia podem ser orientados a consumir alguns derivados do leite e alimentos contendo lactose sem apresentar sintomas de intolerância, enquanto que outros terão que fazer restrição de lactose na dieta.

In most mammals, lactase activity declines on the intestinal wall after weaning, characterizing primary hypolactasia that provokes symptoms of lactose intolerance. The intensity of symptoms of distention, flatulence, abdominal pain and diarrhea varies, according to the amount of ingested lactose, and increases with age. Hypolactasia is genetically determined; nonetheless, a mutation occurred that had made a part of mankind tolerate milk in adulthood. Diagnosis is made by a tolerance test, using the lactose challenge. With the discovery made by the Finns of polymorphism associated with lactase persistence, mainly, in Northern Europe, the genetic test was incorporated as a more comfortable diagnostic tool for the intolerant. In Brazil, 43 percent of Caucasian and Mulatto groups have lactase persistence allele, with hipolactasia more frequently found among Blacks and Japanese. However, in clinical practice people with hypolactasia may be advised to consume certain dairy products and food containing lactose without developing intolerance symptoms, whereas others will need a lactose restriction diet.

Estudio comparativo de dos equipos para el test de H2 en aire espirado / Evaluation of breath H2 measured by means of two different analyzers

El test de hidrógeno (H2) en aire espirado es ampliamente utilizado en el estudio de malabsorción de hidratos de carbono, sobrecrecimiento bacteriano intestinal (SBI) y tiempo de tránsito orocecal (TTOC). Objetivo: Comparar los resultados obtenidos por dos equiposde detección de H2, uno de ellos de introducción reciente en nuestro medio. Material y Métodos: 50 pacientes, edad promedio 38,5 +/- 5,2 años (rango 7-77 años), 40 mujeres, se les realizó el test de H2 en aire espirado en paralelo con ambos equipos bajo métodos estandarizados. En 25 de ellos se investigó la presencia de malabsorción de lactosa, y en los otros 25, la presencia de SBI con lactulosa. Se evaluaron los valores de H2 obtenidos con ambos equipos. Resultados: Las lecturas de H2 con ambos equipos no mostraron diferencias significativas tanto para lactosa (p > 0,1), como para lactulosa (p > 0,5). Tampoco hubo diferencias en el TTOC de los pacientes (90 +/- 33,75 min v/s 90.8 +/- 32,42 min) (p > 1). Se obtuvo un índice de concordancia Kappa de 0,92 entre ambos equipos con el test con lactosa y con lactulosa. Conclusión: El equipo portátil es altamente confiable, entregando resultados con una excelente concordancia con respectoal equipo de referencia.

The hydrogen (H2) breath test (BT) is widely used to investigate carbohydrates malabsorption, small intestinal bacterial overgrowth (SIBO) and orocaecal transit time (OTT). Aim: To compare the results of two hydrogen breath devices, one of them, of recent introduction in our country. Methods: Fifty patients were included, mean age 38.5 +/- 5.2years (range 7-77 yrs), 40 women, H2 BT was performed in parallel with both analyzers under standardized methods. Lactose malabsorption was investigated in 25 patients with lactose, and the presence of SIBO in the resting 25 patients, with lactulose, hydrogen values obtained with both devices were evaluated. Results: No differences were observed between the H2 concentrations for lactose BT (p > 0.1) as well as lactulose BT (p > 0.5)and also between the OTT measured by the two devices (90 +/- 33.75 min. v/s 90.8 +/- 32.42 min) (p > 1). We detected a Kappa concordance index of 0.92 for both equipments. Conclusion: The portable device is highly reliable to detect the presence of breath hydrogen, giving results with an excellent concordance to the reference device.

Single nucleotide polymorphism C/T(-13910), located upstream of the lactase gene, associated with adult-type hypolactasia: validation for clinical practice.

OBJECTIVES: To validate C/T(-13910) polymorphism associated with primary hypolactasia for clinical practice. DESIGN AND METHODS: Lactose breath test and PCR-RFLP for the C/T(-13910) polymorphism were performed. RESULTS: Twenty-seven of 28 patients with genotype CC had positive breath tests; all twenty-two patients with genotypes CT or TT had negative breath tests. Agreement of tests was high (p<0.0001; Kappa Index 0.96). CONCLUSION: C/T(-13910) polymorphism detection may be a new tool for primary hypolactasia diagnosis.

Lactase persistence/non-persistence variants, C/T_13910 and G/A_22018, as a diagnostic tool for lactose intolerance in IBS patients.

BACKGROUND: Irritable bowel syndrome (IBS) is a symptom-based disorder characterized by abdominal pain related to altered bowel habit. We evaluated the predictive power of 2 genetic markers of hypolactasia, C/T_13910 and G/A_22018, in IBS patients with and without lactose intolerance in order to gain insight into the role of lactose intolerance in IBS. METHODS: Seventy five patients (59F/16M, mean age: 49.6+/-14.2 years) with an IBS diagnosis based on Rome II criteria and 272 healthy individuals, where 74 (58F/16M, 54.1+/-10.9 years) were matched-controls, were evaluated. IBS and healthy individuals were genotyped for the C/T_13910 and G/A_22018 polymorphisms nearby the lactase-phlorizin hydrolase gene. Hydrogen breath test (HBT) with gas chromatography was performed in IBS patients to assess for lactose intolerance. RESULTS: Of the 75 IBS patients, 28 (37%) were defined as lactose intolerants. The grade/severity of symptoms after an oral lactose load were positively correlated to the expiratory H2 excretion (P<0.001). Alleles and genotypes frequencies from C/T_13910 and G/A_22018 were not significantly different between IBS patients and control individuals (P>0.05;NS). Presence of the C and G allele were positively associated with a higher expiratory hydrogen excretion and more intense gastrointestinal symptoms (P<0.001). Considering these polymorphisms as a diagnostic test for lactose intolerance in IBS patients, presence of the CC and GG genotypes were estimated to have, a sensitivity of 100% and 96%, respectively; and a specificity of 83% and 79%, positive predictive value of 76% and 73%, and negative predictive value of 100% and 97%. CONCLUSIONS: In IBS patients, genotyping of C/T_13910 and G/A_22018 polymorphisms predicts gastrointestinal symptoms after lactose ingestion and are a diagnostic tool for lactose intolerance.

Test de hidrógeno espirado en el estudio de la malabsorción de lactosa y sobrecrecimiento bacteriano en niños / Hydrogen breath test in the study of lactose malabsorption and intestinal bacterial overgrowth in children

La malabsorción de lactosa (ML) y el sobrecrecimiento bacteriano intestinal (SBI) son hallazgos frecuentes en adultos en Chile, pero su incidencia en pacientes pediátricos no ha sido investigada sistemáticamente. El objetivo fue estudiar la incidencia de ML y SBI en pacientes pediátricos que presentan síntomas gastrointestinal posterior a la ingesta de leche. Se analizó además el efecto de una dieta libre de lactosa en los síntomas. Se incluyeron 149 pacientes; edad promedio 9 años (rango 3-15), 88 por ciento de sexo femenino. Se determinó ML y SBI mediante test de hidrógeno en aire espirado. Se registraron síntomas basales y en 43 pacientes después de un mes de dieta libre de lactosa. Resultados: se observó ML en 95 pacientes y SBI en 42 pacientes. Se detectó SBI en 37 por ciento de pacientes con ML y en 15,5 por ciento de los pacientes con digestión a la lactosa. La aparición de ML se relacionó a la edad de las pacientes (3-7 años= 49 años, 8-11= 69 por ciento, 85 por ciento). Casi todos los pacientes experimentaron desaparición de síntomas luego de dieta libre de lactosa. Conclusiones : La ML y SBI deben sospecharse en niños síntomas gastrointestinales. El tratamiento con dieta libre de lactosa se acompañó de una significativa mejoría de los síntomas

Intolerancia a la lactosa / Lactose intolerance

La intolerancia a la lactosa es frecuente en la edad pediátrica, ya sea primaria de aparición tardía o secundaria a otra patología gastrointestinal. En el lactante se presenta como un cuadro de diarrea aguda a veces con deshidratación y acidosis y en el preescolar y escolar como dolor abdominal recurrente. La prueba del hidrógano espirado es el examen más confiable para hacer el diagnóstico. El tratamiento es la suspensión de la lactosa y su reemplazo por fórmulas lácteas hidrolizadas o fermentadas o productos sin lactosa, cuidando los aportes de calcio para alcanzar los requerimientos