Correlation of G/A -22018 single-nucleotide polymorphism with lactase activity and its usefulness in improving the diagnosis of adult-type hypolactasia among North Indian children

Abstract

Adult-type hypolactasia (AtH or lactase non-persistence) is the physiological decline in lactase activity that manifests in majority of the world's population after weaning. Recently, various single-nucleotide polymorphisms (SNPs) upstream of lactase gene (LCT) have been suggested to be associated with AtH or the lactase persistent trait in different human populations. C/T -13910 SNP was found be completely associated with AtH in Finnish population, and G/A -22018 SNP was found to be strongly, but not completely, associated with AtH. The aim of this study was to correlate G/A -22018 SNP with intestinal lactase activity in North Indian children. These children were also genotyped for C/T -13910 SNP. We also examined the differences in milk consumption and milk-related clinical symptoms in children with different genotypes of G/A -22018 and C/T -13910 SNPs. Intestinal biopsies were obtained from 231 children aged 2-16 years undergoing routine endoscopy for various abdominal complaints. The biopsies were assayed for lactase, sucrase, and maltase activities and genotyped for G/A -22018 and C/T -13910 SNPs using restriction fragment length polymorphism and DNA sequencing analysis. There was a significant correlation between lactase activity and different genotypes of G/A -22018 SNP. Children with G/G -22018 genotype had low lactase activity. With a reference value of <10 U/g protein (lactase activity) to be indicative of AtH, the sensitivity and specificity of genetic test based on G/A -22018 SNP was 94.4 and 94.1 %, respectively. Furthermore, the consumption of milk was lower in children with G/G -22018 genotype. Flatulence was the only symptom significantly more frequent among the children with G/G -22018 genotype compared to those with G/A and A/A -22018 genotypes. However, most of the children with G/G -22018 genotype seem to tolerate small amounts of milk without any significant difference in gastrointestinal symptoms from those with G/A and A/A -22018 genotypes.

13910C>T and 22018G>A LCT gene polymorphisms in diagnosing hypolactasia in children

“…In their paper from 2016, Alliende and colleagues 13 showed that a genetic test based on the LCT ‐13910C>A polymorphism may be used as a good indicator of hypolactasia, and it corresponds to HBT results in children older than 6. The relation between the LCT ‐13910C>T polymorphism and hypolactasia is also well documented by other researchers and in studies conducted among adults and children 5 , 11 , 14 , 17 , 18 …”

“…The relation between the LCT-13910C>T polymorphism and hypolactasia is also well documented by other researchers and in studies conducted among adults and children. 5,11,14,17,18 Previously, the LCT-22018G>A polymorphism was ascribed less significance as regards to controlling the expression of the gene that codes lactase. 18 In some populations, however, it was shown that the 22018G>A polymorphism is a good indicator of PLI -even better than the 13910C>T polymorphism.…”

“…5,11,14,17,18 Previously, the LCT-22018G>A polymorphism was ascribed less significance as regards to controlling the expression of the gene that codes lactase. 18 In some populations, however, it was shown that the 22018G>A polymorphism is a good indicator of PLI -even better than the 13910C>T polymorphism. 19,20 This work proved that both the LCT 13910CC and 22018GG polymorphisms correlate to a positive HBT result in children 6 and older (p ¼ 0.0011 and p ¼ 0.0003).…”

Study on influence of age, gender and genetic variants on lactose intolerance and its impact on milk intake in adult Asian Indians

“…Recent research performed in India using genetic test, lactose tolerance test (LTT) and lactose hydrogen breath test has revealed that À13910C4T acts as a predictor of LM in North Indians and South Indians (Babu et al, 2010). Another study carried out on North Indian children has proved that À22018G4A SNP also acts as a good indicator to detect LNP (Kuchay et al, 2013).…”

Síntomas de intolerancia a la lactosa en consumidores de leche deslactosada comparada con la leche sin lactosa del hospital Hipólito Unanue del 2015

“…El polimorfismo más común asociado con la persistencia de la lactasa en caucásicos se caracteriza por un cambio de C> T en 13910 pares de bases aguas arriba del gen de la lactasa. Varios otros polimorfismos para la persistencia de lactosa se han identificado con diferencias regionales específicas [46][47][48][49][50][51] . Mientras que el genotipo C / C13910 se asocia con malabsorción de lactosa, los genotipos C / T y T / T se encuentran en individuos con persistencia de lactasa 29 .…”