Adult-type hypolactasia (primary lactose malabsorption, lactase non-persistence) is the most common enzyme deficiency in humans, presenting in all populations and varying considerably by frequency in different ethnicities. Adult-type hypolactasia may lead to unspecific abdominal complaints such as diarrhea, flatulence, audible bowel, nausea, bloating and abdominal cramping. The condition is genetically determined and inherited as a recessive trait. Homozygous subjects with the C/C-13910 genotype evince very low lactase activity in the jejunum, whereas heterozygous C/T-13910 subjects and carriers of the T allele in its homozygous variant (T/T-13910) maintain a higher lactase activity.
The possibility of persisting lactase in adult age appeared in humans as a mutation. The genetic test allowing determination of the LNP genotype and thus diagnosing adult-type hypolactasia was discovered in 2002.
The prevalence of adult-type hypolactasia among Northern Russians and indigenous Nenets was studied here using genotyping for LCT gene variants as a marker for the condition. We observed that Northern Russians had a 36% prevalence of adult-type hypolactasia, whereas 90% of neighboring native Nenets are lactase non-persistent.
We also studied the influence of C/C-13910 on the appearance of GI symptoms and milk consumption among a Russian population. The conclusion was that homozygotes for C/C have more GI symptoms caused by milk. Milk was determined as only one of the tested foods giving rise to symptoms in LNP subjects. Moreover, there were fewer milk-consumers among C/C-13910 subjects compared to C/T and T/T genotype carriers.
We discovered the G>A-13914 genotype variant upstream of the LCT gene in one of our study subjects who carried C/C in -13910 position. We examined members of this person`s family and found this mutation in three of them. Previously such a variant had been reported in two persons only, both of them living in Central Europe. However, in the current study the significance of the variant was for the first time investigated and described. We carried out measurement of the lactase activity in the small intestine of our subject and found that a variant in heterozygous state was associated with increased lactase activity, suggesting that this phenomenon was most likely associated with the G>A-13914 variant.
In the Nenets study the method of concordance of grandparents’ origin was applied to establish the number of native Nenets in the study group. We estimated separately the frequency of C/C-13910 among those who had four, three, two and one grandparent of Nenets origin. Such an approach was applied for the first time in a hypolactasia study. It emerged that those who had only Nenets in previous generations had a highest prevalence of hypolactasia, while the frequency among others diminishes gradually in accordance to the number of Nenets ancestors. We used the term ethnicity in the biological sense in our study.
We established that the prevalence of adult-type hypolactasia varies considerably among populations even if they are close geographical neighbors. The frequency of a genotype depends on ethnicity and history of milk usage. The gene flow from other populations exerts an influence on the frequency of lactase non-persistence.