Introducing Genetic Testing for Adult-Type Hypolactasia

Abstract

Background and Aims: To evaluate genotyping for two DNA variants (c.1993+327C>T and c.1438+117G>A), recently found to be associated with adult-type hypolactasia, in the diagnosis of lactose intolerance. Methods: In total, 166 consecutive patients with gastrointestinal symptoms mimicking hypolactasia admitted to the clinic between March 2002 and December 2002 were included. Genotyping for the two DNA variants (c.1993+327C>T and c.1438+117G>A) and standard H₂ breath test was performed. Results: Among 116 patients with positive H₂ breath test, the c.1993+327C variantwas detectablein 106 (91.4%) patients. Among 50 patients with negative H₂ breath test, the c.1993+327Cvariantwas seen in 2 patients. Sensitivity, specificity, positive and negative predictive values for the c.1993+327C variant were 91.4, 96.0, 98.1 and 82.8%, respectively. Genotyping for the c.1438+117G variant did not bring any additional information. Among 4 of the 10 patients with positive H₂ breath test but negative for the c.1993+327C and the c.1438+117G variant,further evaluation revealed other diseases known to cause secondary hypolactasia such as celiac disease and short bowel syndrome. Conclusion: In symptomatic patients, genotyping for the DNA variant c.1993+327C is a reliable test for adult-type hypolactasia with high sensitivity and specificity and thus provides a new tool in the diagnostic workup of hypolactasia.

Correlation between lactose absorption and the C/T-13910 and G/A-22018 mutations of the lactase-phlorizin hydrolase (LCT) gene in adult-type hypolactasia

“…Polymorphism of C/T-13910 has been used as a diagnostic predictor of adult-type hypolactasia in some European countries (5,23,24). However, this polymorphism has not been associated with lactase persistence in some African SubSaharan populations since several milkdrinking groups did not show the T-13910 allele.…”

“…However, it is an invasive test (5). Among non-invasive laboratory exams for the diagnosis of lactose malabsorption, the hydrogen breath test (HBT) is widely used.…”

Polymorphism C/T-13910 of the LCT gene regulatory region and lactase deficiency in Eurasian populations

“…Ранее при исследовании выборок финнов и немцев было показано, что генотип СС по полиморфизму LCT *C/T-13910 является детерминантом гиполактазии [15,19]. Аналогичные результаты получены нами при сопос-…”

“…Выраженность симптомов гиполактазии зависит от индивидуаль-ных физиологических особенностей человека, характера питания, а также состава микрофлоры кишечника. При исключении из диеты цельного молока и переходе на продукты, не содер-жащие лактозу или характеризующиеся пониженным ее содержанием (таковы, например, кисломолочные продукты), у большинства пациентов симптомы гипо-лактазии исчезают [15].…”

Intolerância à lactose: mudança de paradigmas com a biologia molecular

“…Os indivíduos com o genótipo CC apresentaram sintomas de intolerância à lactose, e aqueles com os genótipos CT e TT toleraram a lactose 14 , confirmando os achados publicados em 1973 por Sahi et al de que a intolerância à lactose primária do adulto é traço recessivo. 15 Estudos posteriores no Brasil 16,17,18 e em outros países [19][20][21][22][23][24][25][26] confirmaram a associação desse polimorfismo com a intolerância e tolerância à lactose, exceto na África. 27,28 Essa região LCT-13910C>T funcionou in vitro como elemento cis capaz de aumentar diferentemente a atividade de transcrição do promotor do gene da lactase 29 e se associou significantemente com maior expressão de RNAm do gene LCT na mucosa intestinal dos indivíduos com alelo de persistência da lactase, LCT-13910C>T e LCT-22018G>A, em relação aos que têm genótipo de hipolactasia, sugerindo que a ação seja em nível de regulação de transcrição do gene LCT 30 .…”