Background: Absorption of milk sugar (lactose) is regulated by the activity of lactase enzyme in gut wall. Intestinal lactase activity declines during childhood in majority of human populations leading to adult-type hypolactasia (primary lactose malabsorption), limiting the use of fresh milk due to lactose intolerance. Aim of this study was to correlate lactase expression and activity with C/T -13910 variant in Indian children, determine the age of onset of down-regulation of lactase activity and assess the applicability of the C/T -13910 variant as a diagnostic marker for identifying children genetically inclined to develop adult-type hypolactasia. Methods: Intestinal biopsies were obtained from 176 children aged 1-16. years undergoing routine endoscopy for various abdominal complaints. The biopsies were assayed for lactase, sucrase and maltase activities and genotyped for C/T 13910 variant using PCR-RFLP analysis. The functional effect of the C/T - 13910 variant on expression of lactase mRNA and protein in these children was examined using reverse-transcription PCR and western blotting. Results: Among the 176 children investigated in our study, 56.8% (100/176) carried the C/C - 13910 genotype, which has been associated with the onset of adult-type hypolactasia, while 40.9% (72/176) carried the C/T - 13910 genotype and 2.3% (4/176) the T/T - 13910 genotype. There was a significant correlation between lactase activity and C/T - 13910 variant (p 8 years of age for this genotype. C/C - 13910 genotype was associated with low expression of lactase mRNA and protein compared with C/T genotype. Considering lactase activity of 10. U/g protein as gold standard, predictive value of genetic test based on C/T - 13910 variant for adult-type hypolactasia was 100% in children > 8 years of age. Conclusion: C/T - 13910 cis-acting regulatory variant located - 14. kb upstream of lactase gene (LCT) completely correlates with lactase phenotype in Indian children. The genetic testing for the C/T - 13910 variant may be helpful in the diagnosis of adult-type hypolactasia in Indian children. © 2011 Elsevier B.V.
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