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%.

Several different lactase persistence associated alleles and high diversity of the lactase gene in the admixed Brazilian population.

Adult-type hypolactasia is a common phenotype caused by the lactase enzyme deficiency. The -13910 C>T polymorphism, located 14 Kb upstream of the lactase gene (LCT) in the MCM6 gene was associated with lactase persistence (LP) in Europeans. This polymorphism is rare in Africa but several other variants associated with lactase persistence were observed in Africans. The aims of this study were to identify polymorphisms in the MCM6 region associated with the lactase persistence phenotype and to determine the distribution of LCT gene haplotypes in 981 individuals from North, Northeast and South Brazil. These polymorphisms were genotyped by PCR based methods and sequencing. The -13779*C,-13910*T, -13937*A, -14010*C, -14011*T LP alleles previously described in the MCM6 gene region that acts as an enhancer for the LCT gene were identified in Brazilians. The most common LP allele was -13910*T. Its frequency was highly correlated with European ancestry in the Brazilian populations investigated. The -13910*T was higher (0.295) in southern Brazilians of European ancestry and lower (0.175) in the Northern admixed population. LCT haplotypes were derived from the 10 LCT SNPs genotyped. Overall twenty six haplotypes previously described were identified in the four Brazilian populations studied. The Multidimensional Scaling analysis showed that Belém, in the north, was closer to Amerindians. Northeastern and southern Afro-descendants were more related with Bantu-speaking South Africans whereas the Southern population with European ancestry grouped with Southern and Northern Europeans. This study shows a high variability considering the number of LCT haplotypes observed. Due to the highly admixed nature of the Brazilian populations, the diagnosis of hypolactasia in Brazil, based only in the investigation of the -13910*T allele is an oversimplification.

Lactose maldigestion, calcium intake and osteoporosis in African-, Asian-, and Hispanic-Americans.

Dietary calcium is critical for the development of the human skeleton and likely plays an important role in the prevention of osteoporosis. Dairy products provide approximately three-fourths of calcium consumed in the diet and are the most concentrated sources of this essential nutrient. One obstacle that likely interferes with calcium consumption among many ethnic groups is lactose maldigestion. The real or perceived occurrence of intolerance symptoms after dairy food consumption may cause maldigesters to avoid dairy products. Several investigators have observed a relationship between lactose maldigestion, dietary calcium and osteoporosis in Caucasian populations. Research on ethnically diverse populations is necessary to better understand how lactose maldigestion influences the risk for osteoporosis. Low calcium intakes, a greater than previously thought potential for low bone density and extensive lactose maldigestion among Hispanic-American and Asian-American populations may create an elevated risk for osteoporosis. Dietary management strategies for lactose maldigesters to increase calcium consumption include consuming (1) dairy foods with meals, (2) yogurts, (3) calcium-fortified foods, (4) using lactose digestive aids and (5) including dairy foods daily in the diet to enhance colonic metabolism of lactose.

Milhöes de brasileiros adultos näo toleram um copo de leite / Millions of adult brazilians do not tolerate a glass of milk

O consumo de leite, tendo em vista seu alto valor nutritivo, é muito estimulado, tanto pelos programas nutricionais quanto pelas indústrias de laticínio. Entretanto, deve-se considerar que uma condiçäo muito freqüente no Brasil pode causar intolerância ao leite. Esta é má absorçäo de lactose do adulto (MLA), que é determinada geneticamente e tem prevalência intermediária nos brancos e alta nos nao brancos. O objetivo foi avaliar quantos brasileiros podem ter intolerância a um copo de leite. Os dados populacionais do Brasil foram pesquisados em relaçäo às etnias nas cinco regiöes brasileiras através de dados do Instituto Brasileiro de Geografia e Estatística (Censo de 1991). Foi calculado o número de indivíduos com MLA em cada regiäo através da prevalência previamente conhecida de MLA em cada etnia: 45 por cento dos caucasóides do Sudeste, 37 por cento dos caucasóides do Sul, 85 por cento dos negróides do Sudeste, 68 por cento dos negróides do Sul e 78 por cento dos triíbridos nordestinos. Foi considerado que 65 por cento da populaçäo têm mais do que 15 anos, idade em que a MLA já está definida. Trabalhos anteriores detectaram que 63 por cento dos indivíduos com MLA têm intolerância à lactose (IL) e que nestes a ingestäo de um copo de leite causa intolerância de intensidade média em 48 por cento e grave em 26 por cento. Os resultados mostram que, entre os 144 milhoes de brasileiros, a MLA ocorre em 58 milhöes de adultos (maiores de 15 anos), dos quais 37 milhöes têm IL. Destes, 27 milhöes têm intolerância a um copo de leite, dos quais dez milhöes têm intolerância grave, a qual impede as atividades normais. Esses números permitem concluir que, no mínimo, 27 milhöes de brasileiros, por determinaçäo genética, podem ter sintomas ao ingerir um copo de leite. Além desses, muitos outros que tenham deficiência secundária de lactase conseqüente a várias causas, entre elas a desnutriçäo e as parasitores, podem ocorrer com o aumento do número de intolerantes ao leite. Algumas sugestöes para enfrentar este problema: avisar os brasileiros de que o leite pode causar sintomas e propor alternativas, como leites com baixo teor de lactose e queijos, para os programas nutricionais à base de leite.