The frequency of lactase non-persistence has been determined in a large number
of studies in different populations of the world. The frequency has been shown to vary
between populations, ranging from almost 100% in Thais to below 10% in certain
Northern European populations. These data have been reviewed by Simoons (1978) and
Flatz (1987). A selection of the populations that have been studied are shown in
1.1.7.1.
Table
Various studies have been perfoimed to investigate whether lactose tolerance is an
inherited characteristic. They fall into three categories, namely family studies, twin
studies and population studies. The results of these studies are discussed in the
following sections (also reviewed in Swallow & Harvey, 1993; see appendix).
1.1.7.1. E vid en ce from fam ily studies.
The evidence that lactase persistence is a genetically deteimined polymorphism
comes mainly from family studies. The results of these studies are summarised in Table
1.1.7.1.1. A few of these studies have involved direct determination of lactase activity in
the intestine e.g. Ferguson & Maxwell, 1967. However, the majority of families studied
from a wide variety of geographic regions of the world have been examined using an
indirect lactose tolerance test (discussed section 1.1.6.1). These include progeny of
mixed marriages (Flatz & Rotthauwe, 1971).
Three types of family have been studied: families in which both parents are lactase
persistent (i.e. lactose digestors); families in which one parent is persistent and the other
non-persistent and families in which both parents are non-persistent. The results of all
the family studies detailed in Table 1.1.7.1.1 are summarised in Table 1.1.7.1.2 for each
of the available mating types. The balance of evidence from these family studies is
single gene locus where lactase persistence is dominant to non-persistence, which is
recessive. The only results which conflict with this model come from the occunence of a
few individuals in two of the studies who are lactase persistent despite having two non-
persistent parents. In both the study of Gilat, et ciL, 1973 (4 individuals) and that of Lisker et a!., 1975 in Mexico (4 individuals), the possibility that one or other o f the parents had a secondaiy deficiency of lactase was not excluded, nor was the possibility of
non-patemity. Lisker et al. also suggest that these exceptions may be due to errors in the glucose detection method used (95% accuracy estimated, Lisker et al. 1974). It should be noted that the number of lactose non-digester (intolerant or hypolactasic) progeny is
greater in each case than would have been expected for each type of mating. However
this can readily be explained by ascertainment bias(s) since in almost all the studies
families were ascertained through non-persistent individuals. Sahi, (1974) showed, in
his family study, that the numbers of individuals of each phenotype agreed reasonably
well with expectation when this bias was allowed for.
1.1.7.2. E vidence from twin studies.
Another line of evidence in support of the single gene mode of inheritance was
provided by twin studies (Metneki et al., 1984). In this study o f 102 pairs of Hungarian twins it was found that monozygotic twins showed 100% concordance of lactase
persistence phenotype. In the dizygotic twins the proportions of lactase persistence and
non-persistence phenotype were consistent with expected results (shown in Table
1.1.7.3. E v id en c e fro m p o p u la tio n stu d ie s.
Supporting evidence for monogenetic inheritance is also provided by
population studies in which lactase activities were measured directly on intestinal
material. A trimodal distribution of activities was obseiwed in adult intestinal samples,
when sucrase/lactase ratios in post-moitem tissue (Ho et al., 1982) or lactase/maltase ratios in healthy volunteers (Flatz, 1984) were determined (Figure 1.1.7.3.1). In both
these studies, which in each case involved native Europeans, the frequencies of the
individuals within each of these groups were entirely consistent with the expected
frequency for the two types of homozygotes and a group of heterozygotes (see Table
1.1.7.3.2). The level of activity observed in the putative heterozygotes was
approximately half that of the persistent homozygotes, although both of the groups
concordant discordant persistent / persistent non-persistent / non-persistent persistent / non-persistent Observed 27 11 12 Expected 26.Ü 11.1 12.9 Table 1.1.7.2.1.
The observed frequencies o f the lactase persistence phenotypes in dizygotic tw ins and the expected frequencies calculated from the
population frequency o f lactase non-persistence in the general population o f B udapest, H ungary; assum ing a m onogenetic m odel.
Similai’ results were obtained using the I’requencies detemnined in the two separate
10 LL 8 6 4 2 0 >18 S/L ratio Ho e t al,1982 L/M ratio FlaU,1984 F i g u r e 1.1.7.3.1
H i s t o g r a m s d e m o n s t r a t i n g a tr i- m o d a l d is tr ib u tio n o f la c ta s e a c tiv ity