Genetic testing for adult-type hypolactasia in Italian families.
BACKGROUND
Adult-type hypolactasia is characterized by the inability to digest lactose during adulthood, due to lactase (LCT) deficiency. It is usually diagnosed by the measurement of breath hydrogen increase after a lactose load (breath hydrogen test, BHT). A substitution of C to T at position -13910 bp upstream the LCT gene (rs4988235), in a regulatory region, was found to be strongly associated with the lactase persistence phenotype in North-European populations.


METHODS
We investigated the -13910 C/T polymorphism to determine LCT genotype distribution and to validate genetic testing for adult-type hypolactasia in a Southern European population. A total of 43 children referred for suspected lactose malabsorption were enrolled in the study, their parents and siblings (whole sample=112 individuals) also took the breath test, and all were enrolled for clinical monitoring and genotype determination. In addition, 125 unrelated blood donors from the same geographic area were genotyped for the calculation of allelic frequencies. The frequency of C/C genotypes was 70%.


RESULTS
The correlation between the C/C genotype (which should correspond to lactose non-digesters) and positive BHT in unrelated family founders was significant (chi(2)=16.7, p<0.002). The genetic test compared to the BHT had a sensitivity of 95% and 91% and a specificity of 48% and 55% in adults and children, respectively.


CONCLUSIONS
Low specificity might be due to intrinsic limitations of the standard BHT or to other possible mutations, although no sequence variation was found upon sequencing a 253 bp fragment of the LCT regulatory region in asymptomatic individuals.
Mottes
Monica
M
Department of Mother and Child, Biology and Genetics, University of Verona, Verona, Italy. monica.mottes@univr.it
Belpinati
Francesca
F
Milani
Monia
M
Saccomandi
Daniela
D
Petrelli
Elena
E
Calacoci
Marisa
M
Chierici
Roberta
R
Pignatti
Pier Franco
PF
Borgna-Pignatti
Caterina
C
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005190:Family; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007558:Italy; D043322:Lactase / Q000172:deficiency* / Q000235:genetics; D007787:Lactose Intolerance / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012680:Sensitivity and Specificity
D043322:Lactase