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10
| 3 | 2004
Klinisk Biokemi i Norden
a total of 329 children originating from different
populations showed that the C/C
–13910
genotype
was associated with very low lactase activity (<10
U/g protein and L/S-ratio below 0.2) in the major-
ity of children tested at 8 years of age and in every
child older than 12 years of age. The specificity of
the genetic test was 100% and sensitivity of 93%
confirming that C/C-13910 genotype is associated
with the downregulation of lactase activity during
childhood (14). A question frequently asked by par-
ents and clinicians is; what is the amount of lactose
tolerated in adult-type hypolactasia? We did not
find any significant difference in symptoms from
milk between children with the C/C
–13910
genotype
and those with the non-C/C
–13910
genotype accord-
ing to the results of a questionnaire survey. Children
with the C/C
–13910
genotype, however, consumed
significantly less milk compared to children with
the non-C/C-13910 genotype (14). These prelimi-
nary data reflect the complexity of abdominal
complaints due to milk seen also in earlier studies
(5,6).
Implications for genetic testing
Based on the excellent correlation between lactase
enzyme activity and LTT with the C/T
–13910
-
genotypes in several populations (including > 30
global populations; unpublished results) as well as
the reported evidence for an enhancer effect of the
genomic region containing C/T-13910 variant in
functional studies, genotyping of C/T-13910 variant
can be used as a primary screening test of lactose
malabsorption in clinical practice. Genetic test is eas-
ily performed with a semi-automated analysis from
a drop of peripheral blood (EDTA tube) without fast-
ing (18). Compared to traditional tests (LTT, breath
hydrogen test, intestinal biopsy) genetic testing is
more comfortable for a patient and saves time and
costs in health care. Interpretation of the genotyp-
ing result is easier in the laboratory compared to
indirect tests and is done once in a lifetime. It has
to be emphasized, however, that interpretation of the
genetic test is still a challenge in clinical practice due
to poor correlation between symptoms and lactase
activity (see above). Consequently, the result of the
genetic test has to be interpreted individually in
every patient. Genetic testing of lactose malabsorp-
tion is also reliable in diabetes patients whose glu-
cose levels might be affected by the disease in LTT.
When testing children, the age at which the down
regulation takes place has to considered (14). The
result of genetic test does not always reflect lactase
activity in children less than 12 years of age. It is,
however, valuable in excluding lactose malabsorp-
tion at all ages. Since 82% -99% of the populations
in Scandinavian countries are lactase persistent
having C/T-13910 or T/T-13910, is it more probable
that these genotypes are detected than C/C
–13910
also in children. If a child has C/C-13910 genotype
it is not recommended to totally avoid lactose (milk
products), since it might have an undesired effect
on the child’s nutrition (19). In the Finnish study
(14) parents had a positive attitude towards genetic
testing of adult-type hypolactasia in their children
further supporting the usefulness and acceptance of
the test as a first stage screening method for adult-
type hypolactasia.
Conclusions
Identification of the DNA variant associated with
lactose malabsorption has facilitated genetic test-
ing as well as functional studies to understand the
evolution of lactase persistence in humans and to
trace the origin of the mutation in human history.
Screening of adult-type hypolactasia in primary
health care is important in diagnosis of abdominal
complaints in populations like those of Northern
Europeans where the prevalence of adult-type
hypolactasia is relatively high and consumption of
dairy products common.
Figure 2
A single nucleotide polymorphism (SNP) C to T associ-
ated with lactase
nonpersistent/persistent trait.
