Avaliação da concordância entre os resultados da genotipagem do polimorfismo C/T-13910 e do teste de tolerância à lactose: um estudo retrospectivo populacional no Brasil / Evaluation of agreement between c/t-13910 polymorphism genotyping results and lactose tolerance test results: a retrospective population-based study in brazil

ABSTRACT 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.

RESUMO Contexto: O teste de tolerancia à lactose (TTL) é ampliamente utilizado por ser minimamente invasivo e de baixo custo, disponível na atenção primária e muito útil na prática clínica. Está bem estabelecido o polimorfismo C/T-13910 na persistência da lactase em populações caucasianas, mas não há estudos avaliando a concordância entre os resultados da genotipagem do polimorfismo C/T-13910 e do TTL no Brasil, onde a população é altamente miscigenada. Objetivo: Avaliar a concordância entre a presença do polimorfismo C/T-13910 e a má absorção nos resultados do TTL. Métodos: Análise retrospectiva de dados coletados de um laboratorio presente em vários estados brasileiros. Os resultados dos pacientes que realizaram um teste genético para intolerância à lactose (genotipagem do polimorfismo C/T-13910) e um TTL de abril de 2016 a fevereiro de 2019 foram analisados para avaliar a concordância entre os testes. Os grupos foram classificados de acordo com a idade (<10 anos; 10-17 anos, ≥18 anos) e estado de residência (São Paulo ou Rio Grande do Sul). Resultados: Entre os 404 pacientes avaliados, houve concordância entre os resultados de genotipagem e TTL em 325 (80,4%) pacientes e discordância em 79 (19,6%) pacientes (K=0,42 - concordância moderada). Em relação ao genótipo, 47 pacientes com genótipo C/C (não persistência de lactase) apresentaram TTL normal e 32 com genótipo C/T ou T/T (indicando persistência da lactase) apresentaram TTL anormal. A idade e o estado de residência (Rio Grande do Sul ou São Paulo) não afetaram a concordância entre os resultados dos exames. Conclusão: Considerando a concordância moderada entre a genotipagem do polimorfismo C/T-13910 e os resultados de TTL (κ=0,42) na população brasileira, sugerimos que a análise de outros polimorfismos poderia ser uma estratégia para melhorar a concordância entre os testes.

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.

The clinical value of Mood glucose and insulin detection in early period of pregnancy on predicting abnormal glucose metabolism / 中国医师进修杂志

Objective To investigate the correlation of fasting plasma glucose (FPG) in early period of pregnancy and abnormal glucose metabolism during gestation period.Methods Two hundred and seventy-seven women with single pregnancy and non-propregnant diabetes mellitus were selected.FPG,fasting insulin,insulin resistance index were detected in early period of pregnancy ( ＜19 weeks).One hundred g oral glucose tolerant test (OGTT) was taken during 24-36 weeks.According to OGTT,patients were divided into gestational impaired glucose tolerance (GIGT) group (24 cases),gestational diabetes mellitus(GDM) group(23 cases),OGTT 1 h higher blood glucose (HG-1) group (26 cases) and normal group (204 cases).Results FPG,fasting insulin and insulin resistance index of GDM group and HG-1 group were obviously higher than those of normal group [( 4.58 ± 0.36 ),( 4.58 ± 0.38) mmol/L vs.( 4.20 ±0.33) mmol/L,(9.4 ± 1.1),(9.3 ±2.1) U/L vs.(7.0 ± 2.1) U/L,2.0 ± 0.4,2.0 ± 0.3 vs.1.3 ± 0.4,P＜ 0.05].FPG of GIGT group [(4.45 ±0.36) mmol/L] was higher than that of normal group (P ＜0.05).After controlled age,body mass index,family history of type-2 diabetes mellitus and sport exercises,the relative risk degree of blood glucose metabolism had correlation with FPG,fasting insulin and insulin resistance index in early period of pregnancy (P ＜ 0.05).Conclusion FPG,fasting insulin and insulin resistance index in early period of pregnancy can predict abnormal glucose metabolism.

Clinical and laboratory study on lactose malabsorption in children / 第三军医大学学报

Lactose tolerance test with ethanol(LTTE)described by Arola was performed in 41 healthy children and lactose malabsorption(LM)could be diagnosed if blood galactose(B-gal)was less than 0.3 mmol/L or urine galactose less than 2 mmol/L.Then 138 healthy infants and children and 95 children with acute diarrhea were examined for LM or lactose intolerance(LI)with the urine samples of LTTE and symptom-response score(SRS).It was found that LTTE was reliable in the diagnosis of LM ;the incidence of LM or LI increased with the increase of age in children)and RV enteritis was liable to be complicated with LM or Li.

The indirect diagnosis for lactase deficiency / 实用儿科临床杂志

0.1), there is not significant difference between them. Comparing with blood method, the sensitivity and specificity of urine method are 94 .1 % and 91. 6 % respectively.Conclusions To determine the B-gal and U-gal, O-toluidine method can be regarded as an indirect diagnostic method of LD.