Hypomorphic variants of lactase-phlorizin hydrolase in congenital lactase deficiency are trafficking incompetent and functionally inactive.

Patients with the rare autosomal recessive disorder congenital lactase deficiency (CLD) present with severe, potentially life-threatening symptoms shortly after birth. Several variants have been characterized within the gene for lactase-phlorizin hydrolase (LCT) that are associated with CLD. Here, we analyze at the biochemical and cellular levels LCT mutants harboring the genetic variants p.Y1390*, p.E1612*, p.S1150Pfs*19, p.S1121L, p.R1587H, and p.S688P. Our data unequivocally demonstrate that these mutants are absolutely transport incompetent, some of which are readily degraded, and are enzymatically inactive. The current study contributes to and expands our understanding on the pathogenesis of CLD at the molecular level.

Development of a novel SNP assay to detect lactase persistence associated genetic variants.

BACKGROUND: In adulthood the activity of the lactase enzyme is inherited as autosomal dominant form associated to Single nucleotide polymorphisms (SNPs). The present research was aimed to develop a novel genetic method to test lactase non persistence more powerfully. METHODS AND RESULTS: In our study, we selected eight different SNPs that are associated with lactase persistence from Caucasian, Arabian Bedouins, sub-Saharian Africans and Asian populations to set up an approach to detect all the eight different SNPs at the same time in the same sample. This technique is centred on the identification of SNPs with a single nucleotide primer extension method using Sanger sequencing and capillary electrophoresis. CONCLUSIONS: Our method allowed us to check the genotype asset of eight SNPs related to lactase persistence simultaneously and in a very efficient manner. It could be applied to a higher number of SNPs in a single reaction.

Fermented foods and probiotics: An approach to lactose intolerance.

The aim of this review was to present various topics related to lactose intolerance with special attention given to the role of fermented foods and probiotics in alleviating gastrointestinal symptoms. Lactose intolerance is a common digestive problem in which the human body is unable to digest lactose, known as milk sugar. Lactose intolerance can either be hereditary or a consequence of intestinal diseases. Recent work has demonstrated that fermented dairy products and probiotics can modify the metabolic activities of colonic microbiota and may alleviate the symptoms of lactose intolerance. We suggest that, lactose free dairy products could be recommended as alternatives for the alleviation of lactose intolerance and for the promotion of human health and wellness.

Colonic mucosal eosinophilia in children without inflammatory bowel disease.

Children undergoing colonoscopy and mucosal biopsies may show increased colonic mucosal eosinophils, which may or may not be associated with inflammatory bowel disease. There is not much clinical data on American children who have isolated increased colonic mucosal eosinophils. We sought to study the clinical correlates of children without inflammatory bowel disease who show increased mucosal eosinophils to understand their clinical presentation, etiological associations, and outcome. A retrospective analysis of children seen at a tertiary-level Children's hospital was performed by reviewing their medical charts and extracting pertinent data. There were 110 children in the study who had increased colonic mucosal eosinophils. Most children presented with abdominal pain, but several of them also had constipation, blood in stools, and diarrhea. Food allergies, irritable bowel syndrome, asthma, and lactase deficiency were the top four conditions present in these patients. Pathology of the colonic distribution revealed involvement of more than two colonic regions in 86% of the subjects, and only two subjects showing epithelial or crypt involvement by eosinophils. All subjects had a good outcome. Children with colonic mucosal eosinophilia (CME) who do not have an inflammatory bowel disease most frequently present with abdominal pain and primarily an increase of lamina propria eosinophils in two or more colonic regions. Based on the etiological associations we noted in the study, a work-up of children with CME may encompass detailed history for functional gastrointestinal disorders and lactose intolerance, testing for food and environmental allergies, stool examination for parasites, and peripheral blood counts. Almost all children had resolution of symptoms in the studied period suggesting that CME in children has a good clinical outcome.

Effects of Prebiotic and Probiotic Supplementation on Lactase Deficiency and Lactose Intolerance: A Systematic Review of Controlled Trials.

Lactose intolerance (LI) is characterized by the presence of primarily gastrointestinal clinical signs resulting from colonic fermentation of lactose, the absorption of which is impaired due to a deficiency in the lactase enzyme. These clinical signs can be modified by several factors, including lactose dose, residual lactase expression, concurrent ingestion of other dietary components, gut-transit time, and enteric microbiome composition. In many of individuals with lactose malabsorption, clinical signs may be absent after consumption of normal amounts of milk or, in particular, dairy products (yogurt and cheese), which contain lactose partially digested by live bacteria. The intestinal microbiota can be modulated by biotic supplementation, which may alleviate the signs and symptoms of LI. This systematic review summarizes the available evidence on the influence of prebiotics and probiotics on lactase deficiency and LI. The literature search was conducted using the MEDLINE (via PUBMED) and SCOPUS databases following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and included randomized controlled trials. For each study selected, the risk of bias was assessed following the Cochrane Collaboration methodology. Our findings showed varying degrees of efficacy but an overall positive relationship between probiotics and LI in relation to specific strains and concentrations. Limitations regarding the wide heterogeneity between the studies included in this review should be taken into account. Only one study examined the benefits of prebiotic supplementation and LI. So further clinical trials are needed in order to gather more evidence.

Colonic mucosal inflammatory cells in children and adolescents with lactase deficiency.

INTRODUCTION AND OBJECTIVES: Many of the symptoms of patients with lactose intolerance are due to fermentation of undigested lactose in the colonic lumen, which may also lead to inflammatory cell changes in the colonic mucosa. The objective of our project was to understand the histopathological changes involving infiltration of eosinophils and mast cells in the colonic mucosa of children with lactase deficiency (LD). METHODS: In this retrospective study we studied colonic mucosa of children and adolescents with LD to determine if any pathological changes or inflammatory cell changes were present. Pathology reports and Hematoxylin and eosin stained slides were reviewed. Tryptase immunohistochemistry was performed for mast cell assessment. RESULT: There were 30 subjects in the study who had a LD and 15 presented with diarrhea and 15 without diarrhea. The colonic mucosa of 35.5 % of the subjects revealed increased mucosal eosinophils. There was no increase of mast cells or lymphocytic colitis in any of the subjects. Excepting for the increased eosinophils in a subset of the subjects, all had a normal appearance of the colonic mucosa. CONCLUSION: Colonic mucosa of children and adolescents with LD has a normal histological appearance in majority of the patients. However, 35 % of the patients could demonstrate elevated eosinophils. In primary LD without any comorbidity there is no increase of mast cells and lymphocytic cells in the colonic mucosa.

Clinical and Histopathologic Predictors of Disaccharidase Deficiency in Duodenal Biopsy Specimens.

OBJECTIVES: Disaccharidase (DS) activity in duodenal biopsy specimens is the gold standard for diagnosing DS deficiency. We investigated strategies to reduce the need for DS testing and whether clinical or histopathologic factors predict DS deficiency. METHODS: A retrospective chart review analyzed 1,678 DS results in children, biopsy indication(s), and duodenal histopathology. RESULTS: One or more DSs were abnormal in 42.8%. Sufficient lactase predicted sucrase, palatinase, and maltase sufficiency (negative predictive value 97.7%). Three patients had sucrase-isomaltase deficiency (0.2%). DS deficiency was more common in biopsy specimens for positive celiac serology (78.0%). Villous blunting, intraepithelial lymphocytosis, and active inflammation predicted DS deficiency; a combination of any two had an 81.4% positive predictive value. CONCLUSIONS: Utilization could be reduced by only testing cases with normal duodenal histopathology and ongoing clinical suspicion for DS deficiency after reviewing pathology. In cases with suspected celiac disease and/or mucosal injury, DS deficiency is common and likely secondary, limiting test utility.

Lactose intolerance, lactose malabsorption and genetic predisposition to adult-type hypolactasia in patients after restorative proctocolectomy.

This study provides up-to-date findings on lactose malabsorption, lactose intolerance and genetic predisposition to adult-type hypolactasia in 72 patients after restorative proctocolectomy (RPC). The lactose malabsorption was assessed by hydrogen-methane breath test. Genetic predisposition to adult-type hypolactasia was assessed by detecting -13910T/C polymorphism in the lactase gene. Lactose intolerance was more frequent in UC (ulcerative colitis) patients than FAP (familial adenomatous polyposis) patients (77.5% vs. 55.2%; p=0.01). The C/C genotype of the lactase gene was observed in 39.1% subjects with no significant difference between UC and FAP patients. Lactose malabsorption occurred in 10.1% of subjects and almost only in patients with genetic predisposition, with the same frequency in UC and FAP patients.

[Birth-cohort analysis in adult-type hypolactasia]. / A felnottkori hypolactasia születésikohorsz-vizsgálata.

INTRODUCTION AND AIM: To assess the prevalence of lactase gene promoter C/T13910 phenotypes in patients with lactose intolerance symptoms and to analyze the birth-cohort phenomenon in lactose-intolerant patients. METHOD: 1266 patients consulted between 2010 and 2017 were enrolled. Five-year cohort periods of patients born before 1939 and after 1995 were defined and the prevalence of C/T13910 phenotypes was calculated. C/T13910 phenotypes were determined by polymerase chain reaction. RESULTS: The prevalence of the CC phenotype was 43.1%, TC was detected in 44.3% and TT in 12.6% of the cases. The prevalence of the CC phenotype showed a non-linear incremental increase in females, from 9.13% in those born before 1939 to 37.7% in those born after 1995. CONCLUSION: The prevalence of CC phenotype raised incrementally in females, suggesting a gender/hormonal influence. Orv Hetil. 2019; 160(14): 549-554.

Karyotyping and population genetics in Cold War Mexico: Armendares's and Lisker's characterization of child and indigenous populations, 1960s-1980s.

This paper focuses on geneticists Salvador Armendares's and Rubén Lisker's studies from the 1960s to the 1980s, to explore how their work fits into the post-1945 human biological studies, and also how the populations they studied, child and indigenous, can be considered laboratories of knowledge production. This paper describes how populations were considered for different purposes: scientific inquiry, standardization of medical practices, and production or application of medicines. Through the narrative of the different trajectories and collaborations between Armendares and Lisker, this paper also attempts to show the contact of their scientific practices, which brought cytogenetics and population genetics together at the local and global levels from a transnational perspective.

Effects of Bifidobacterium longum and Lactobacillus rhamnosus on Gut Microbiota in Patients with Lactose Intolerance and Persisting Functional Gastrointestinal Symptoms: A Randomised, Double-Blind, Cross-Over Study.

Functional gastrointestinal symptoms are frequent, and may be driven by several pathogenic mechanisms. Symptoms may persist in lactose intolerant (LI) patients (i.e., subjects with intestinal lactase deficiency, lactose malabsorption producing symptoms), after a lactose-free diet. Our hypothesis was that probiotic and vitamin B6 treatment may be useful to alleviate symptoms in LI patients through a positive modulation of gut microbial composition and relative metabolism. We aimed to test the efficacy of a novel formulation of Bifidobacterium longum BB536 and Lactobacillus rhamnosus HN001 plus vitamin B6 (ZR) in 23 LI subjects with persistent symptoms during a lactose-free diet. Symptoms, microbiome, and metabolome were measured at baseline and after 30 days in a crossover, randomized, double-blind study of ZR versus placebo (PL). Compared with PL, the administration of probiotics and vitamin B6 significantly decreased bloating (p = 0.028) and ameliorated constipation (p = 0.045). Fecal microbiome differed between ZR and PL. ZR drove the enrichment of several genera involved in lactose digestion including Bifidobacerium. Moreover, the relative abundance of acetic acid, 2-methyl-propanoic acid, nonenal, and indolizine 3-methyl increased, while phenol decreased. Our findings highlight the importance of selected probiotics and vitamin B6 to alleviate symptoms and gut dysbiosis in lactose intolerant patients with persistent functional gastrointestinal symptoms.

Congenital Lactase Deficiency: Mutations, Functional and Biochemical Implications, and Future Perspectives.

Congenital lactase deficiency (CLD) is a severe autosomal recessive genetic disorder that affects the functional capacity of the intestinal protein lactase-phlorizin hydrolase (LPH). This disorder is diagnosed already during the first few days of the newborn's life due to the inability to digest lactose, the main carbohydrate in mammalian milk. The symptoms are similar to those in other carbohydrate malabsorption disorders, such as congenital sucrase-isomaltase deficiency, and include severe osmotic watery diarrhea. CLD is associated with mutations in the translated region of the LPH gene that elicit loss-of-function of LPH. The mutations occur in a homozygote or compound heterozygote pattern of inheritance and comprise missense mutations as well as mutations that lead to complete or partial truncations of crucial domains in LPH, such as those linked to the folding and transport-competence of LPH and to the catalytic domains. Nevertheless, the identification of the mutations in CLD is not paralleled by detailed genotype/protein phenotype analyses that would help unravel potential pathomechanisms underlying this severe disease. Here, we review the current knowledge of CLD mutations and discuss their potential impact on the structural and biosynthetic features of LPH. We also address the question of whether heterozygote carriers can be symptomatic for CLD and whether genetic testing is needed in view of the severity of the disease.

Karyotyping and population genetics in Cold War Mexico: Armendares's and Lisker's characterization of child and indigenous populations, 1960s-1980s / Cariotipia e genética de populações no México da Guerra Fria: as caracterizações de Armendares e Lisker sobre as populações infantil e indígena, 1960-1980

Abstract This paper focuses on geneticists Salvador Armendares's and Rubén Lisker's studies from the 1960s to the 1980s, to explore how their work fits into the post-1945 human biological studies, and also how the populations they studied, child and indigenous, can be considered laboratories of knowledge production. This paper describes how populations were considered for different purposes: scientific inquiry, standardization of medical practices, and production or application of medicines. Through the narrative of the different trajectories and collaborations between Armendares and Lisker, this paper also attempts to show the contact of their scientific practices, which brought cytogenetics and population genetics together at the local and global levels from a transnational perspective.

Resumo Aborda o trabalho dos geneticistas Salvador Armendares e Rubén Lisker, entre 1960 e 1980, para analisar como se insere nos estudos biológicos humanos do pós-1945, e demonstra como as populações estudadas por eles, a infantil e a indígena, podem ser consideradas laboratórios de produção de conhecimento. O artigo revela como as populações foram consideradas para diversos propósitos: investigação científica, padronização das práticas médicas e produção ou aplicação de suas medicinas. Por meio da narrativa das diferentes trajetórias e colaborações entre Armendares e Lisker, também procura discutir o contato de suas práticas científicas, que colocaram a citogenética e a genética de populações lado a lado nos níveis local e global a partir de uma perspectiva transnacional.

Assessment of lactase activity in humans by measurement of galactitol and galactonate in serum and urine after milk intake.

Background: Lactase is an enzyme that hydrolyzes lactose into glucose and galactose in the small intestine, where they are absorbed. Hypolactasia is a common condition, primarily caused by genetic programming, that leads to lactose maldigestion and, in certain cases, lactose intolerance. Galactitol and galactonate are 2 products of hepatic galactose metabolism that are candidate markers for the intake of lactose-containing foods. Objectives: The primary objective of the study was to explore the changes in serum and urine metabolomes during postprandial dairy product tests through the association between lactase persistence genotype and the postprandial dynamics of lactose-derived metabolites. Methods: We characterized the 6-h postprandial serum kinetics and urinary excretion of lactose, galactose, galactitol, and galactonate in 14 healthy men who had consumed a single dose of acidified milk (800 g) which contained 38.8 g lactose. Genotyping of LCT-13910 C/T (rs4988235) was performed to assess primary lactase persistence. Results: There were 2 distinct postprandial responses, classified as high and low metabolite responses, observed for galactose, and its metabolites galactitol and galactonate, in serum and urine. In all but 1 subject, there was a concordance between the high metabolite responses and genetic lactase persistence and between the low metabolite responses and genetic lactase nonpersistence (accuracy 0.92), galactitol and galactonate being more discriminative than galactose. Conclusions: Postprandial galactitol and galactonate after lactose overload appear to be good proxies for genetically determined lactase activity. The development of a noninvasive lactose digestion test based on the measurement of these metabolites in urine could be clinically useful. This trial was registered at clinicaltrials.gov as NCT02230345.

Treatment of lactase deficiency in children's obesity with genotype c/c 13910 of lactase gene.

OBJECTIVE: 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. PATIENTS AND METHODS: 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: 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. CONCLUSION: 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.

Real-time PCR based detection of the lactase non-persistence associated genetic variant LCT-13910C>T directly from whole blood.

Primary hypolactasia is the main cause of lactose intolerance in adults. It is strongly associated with the single genetic variant LCT-13910C>T, located upstream of the lactase encoding gene. Consequently, analysis of LCT-13910C>T has been recommended as a direct genetic test for the trait. The aim of our study was to develop a TaqMan probe based real-time PCR protocol for the detection of the LCT-13910C>T variant directly from whole blood, circumventing DNA isolation. The LCT-13910C>T variant was determined using the DirectBlood Genotyping PCR Kit (myPOLS Biotec, Konstanz, Germany) together with an in-house TaqMan primer-probe assay. Validity and specificity of the assay was evaluated using EDTA anti-coagulated whole blood samples and corresponding DNA samples. Results from real-time PCR were compared with results obtained by Sanger sequencing from 105 blinded whole blood samples. Validity and specificity of the assay using whole blood were comparable to those using purified genomic DNA as substrate in PCR. Genetic analysis of blood samples were in complete agreement with results obtained by Sanger sequencing. In conclusion, we present a reliable real-time PCR protocol for the detection of the LCT-13910C>T variant directly from whole blood further facilitating diagnosis of primary hypolactasia in symptomatic patients.

Maternal Lactase Polymorphism (rs4988235) Is Associated with Neural Tube Defects in Offspring in the National Birth Defects Prevention Study.

BACKGROUND: The risk of neural tube defect (NTD)-affected pregnancies is reduced with adequate folic acid intake during early pregnancy. However, NTDs have been observed among offspring of women with adequate folic acid intake. Some of these women are possibly not absorbing enough folic acid. Because lactase deficiency can lead to poor nutrient absorption, we hypothesized that lactase-deficient women will be at increased risk of having offspring with NTDs. OBJECTIVE: We examined the association between maternal rs4988235 (a lactase deficiency genetic marker) and NTDs in offspring. METHODS: We conducted a case-control study using data from the National Birth Defects Prevention Study, United States, 1997-2009, restricting to non-Hispanic white (NHW) and Hispanic women. Cases were women with an offspring with an NTD (n = 378 NHW, 207 Hispanic), and controls were women with an offspring without a birth defect (n = 461 NHW, 165 Hispanic). Analyses were conducted separately by race/ethnicity, using logistic regression. Women with the CC genotype were categorized as being lactase deficient. To assess potential effect modification, analyses were stratified by lactose intake, folic acid supplementation, dietary folate, and diet quality. RESULTS: Among NHW women, the odds of being lactase deficient were greater among cases compared with controls (OR: 1.37; 95% CI: 1.02, 1.82). Among Hispanic women, the odds of being lactase deficient were significantly lower among cases compared with controls (OR: 0.50, 95% CI: 0.33, 0.77). The association differed when stratified by lactose intake in NHW women (higher odds among women who consumed ≥12 g lactose/1000 kcal) and by dietary folate in Hispanic women (opposite direction of associations). The association did not differ when stratified by folic acid supplementation or diet quality. CONCLUSIONS: Our findings suggest that maternal lactase deficiency is associated with NTDs in offspring. However, we observed opposite directions of effect by race/ethnicity that could not be definitively explained.

Digestive side-effects with teriflunomide: Thoughts on lactose.

INTRODUCTION: Teriflunomide, a novel, orally bioavailable, active metabolite of leflunomide, has anti-inflammatory activity. It is prescribed as a first-line treatment for relapsing-remitting multiple sclerosis (RRMS) at a dose of one 14mg tablet per day. Common adverse reactions observed in placebo-controlled trials with a frequency≥10% and a rate twofold or more than reported with placebo, include digestive disorders. As teriflunomide tablets also contain lactose, the official recommendations are clear about not prescribing this drug to patients with known lactose intolerance and those with rare hereditary problems due to galactose intolerance. METHODS: Our study systematically collected, from our MS clinical practice, all adverse events presenting in the first 100 patients treated with teriflunomide. All of these patients were systematically asked if they were known to have lactose intolerance. RESULTS: None of these 100 patients declared having known, documented lactose intolerance. Yet, after starting teriflunomide, 14 reported mild-to-moderate diarrhea, which resolved within a month, but four of these patients continued to have daily diarrhea (grade 2 WHO classification), prompting us to perform a lactose breath test (LBT) for malabsorption. All four tested positive and were therefore diagnosed with lactose intolerance. Digestive symptoms were resolved with probiotics, and teriflunomide was maintained in three cases; the fourth patient decided, despite the adverse event being resolved, to stop taking teriflunomide. CONCLUSION: In cases of prolonged digestive side-effects after the introduction of teriflunomide, a lactose-malabsorption breath test should be proposed to confirm the culpability or not of an enzymatic defect in the occurrence of adverse events.

Association between increased plasma levels of homocysteine and depression observed in individuals with primary lactose malabsorption.

BACKGROUND: Current literature proposes associations between homocysteine (HCY), folic acid (FA), vitamin B12 metabolism and depression. However, the exact underlying biological mechanisms remain unclear. This study aimed at evaluating a possible link between primary adult-type lactose malabsorption (PALM), HCY, FA and vitamin B12 metabolism and depressive disorder. METHODS: Plasma levels of HCY, FA and vitamin B12 were determined in 78 patients with PALM and 160 individuals with lactase persistence sub-grouped by the presence or absence of major depression. RESULTS: In 78 patients with PALM, the subgroup of 22 individuals with major depression showed significantly higher median (interquartile range) HCY (10.10 [8.46-12.03] vs. 8.9 [7.54-9.86] µmol/L, p = 0.029) and lower plasma FA levels (5.7 [4.68-9.14] vs. 6.95 [5.24-10.56] µmol/L, p = 0.272) compared to the subgroup of 56 individuals without depression, respectively. No such associations could be observed for those 160 individuals without PALM (i.e., lactase persistence) Plasma HCY levels were positively correlated with depressive symptoms (p = 0.052), and showed negative correlations with FA (p = < 0.001) and vitamin B12 (p = 0.029), respectively. CONCLUSION: Depressed individuals with PALM were found with significantly higher HCY and lower FA levels compared to non-depressed individuals with PALM, however, this association was absent in the subgroup of lactase persistent individuals. These findings suggest an association between increased HCY levels, lactose malabsorption and depression.

Does primary lactase deficiency reduce bone mineral density in postmenopausal women? A systematic review and meta-analysis.

Postmenopausal osteoporosis is a significant cause of morbidity and mortality. The role of primary lactase deficiency (PLD) in its development is not clear. This meta-analysis showed that PLD is a risk factor for osteoporosis in postmenopausal women. These women need special attention in terms of screening for osteoporosis and its prevention. INTRODUCTION: Postmenopausal osteoporosis is an important predictor of bone fractures. The purpose of the study was to conduct a systematic review and meta-analysis of association of PLD and bone mineral density (BMD) in postmenopausal women. METHODS: The electronic databases PubMed, Scopus, and Web of Science were searched over the course of July 2017 for any date of publication without language limitation. Studies were included in the meta-analysis if the diagnosis of PLD was made by genetic testing or H-2 breath tests and the diagnosis of osteoporosis was made by a modern reliable method for BMD measurement. Two investigators conducted a comprehensive, independent review of all the papers. Five of the studies initially identified met the inclusion criteria. We used MOOSE guidelines for abstracting data and assessing data quality and validity. Meta-analysis was performed using the random effects model. RESULTS: Five case-control studies with 2223 participants and 763 lactase-deficient cases fulfilled the inclusion criteria. Meta-analysis showed a significantly higher bone density Z-score in absorbers (mean difference 0.20, CI (0.14-0.27), P = 0.000), with no significant heterogeneity among the studies. Moreover, the Z-score in the vast majority of the measured sites (femoral head, femoral neck, lumbar spine, radius, and Ward's triangle) was significantly higher in absorbers. There was no significant overall difference in BMD in g/cm2 between absorbers and non-absorbers, but a significantly higher BMD using g/cm2 was observed in absorbers in the total hip site. CONCLUSIONS: Postmenopausal women with PLD had lower Z-scores at most anatomic sites compared to healthy controls.