Genetic Components of Lactose Intolerance and Community Frequency

To the Editor: We read with interest the report by Obermayer-Pietsch published in the January issue of the Journal.1 Obermayer-Pietsch et al.1 showed that the genetic predisposition for adult-type lactose intolerance (C/C-13910 variant) is a risk factor for reduced BMD and nonvertebral bone fractures. In total, 54 of 258 (21%) postmenopausal women carried the C/C-13910 variant. These women have to be considered as lactose intolerant. Noteworthy, only 27% of this 54 women with the C/C-13910 variant were aware of their lactose intolerance. The majority of these patients seemed to reduce their intake of lactose/milk unconsciously because of the resulting symptoms after lactose ingestion and might therefore call themselves as lactose tolerant. These data confirm and extend previous results implicating that patients with known lactose intolerance who therefore avoid lactose-containing products are at higher risk for fractures and display a reduced bone peak mass.2, 3 Interestingly, in the study by Obermayer-Pietsch et al., the homozygous C/C-13910 genotype was not the only genotype associated with an increased risk for reduced BMD. Moreover, women with the heterozygous T/C-13910 genotype also had reduced BMD and showed a trend for increased fracture risk. If both the C/C-13910 variant and the T/C-13910 variant are associated with decreased activity of the LPH gene, this would indicate that ∼72% of Austrian women have an impaired ability to digest milk and/or milk products. This would have major implications for the general dietary recommendations in this population. Although the data for the heterozygous T/C-13910 genotype are not as impressive as the data for the homozygous C/C-13910 genotype, the authors didn't comment on these results in their discussion. Indeed, because of the present knowledge of the genetic and molecular basis of primary lactose intolerance, these findings are conflicting. In our own experience, we analyzed the frequency of the C/C-13910 genotype in 187 controls. The C/C-13910 genotype, the C/T-13910 genotype, and the T/T-13910 genotype were found in 21%, 50%, and 29%, respectively.4 Seventy-nine percent of healthy controls carrying al least one T allele are thought to be lactose tolerant. This is in agreement with the previous reported frequency of lactose tolerance in the German population.5 These data are supported from various functional studies: Kuokkanen et al.,6 who showed that the presence of at least one T−13910 or A−22018 allele is sufficient to express an adequate amount of LPH mRNA (lactase-p-hydrolase, the gene encoding for the lactase enzyme) and higher lactase activities (>13 U/g) in the intestinal mucosa. In addition, two recent in vitro studies indicate that the T-13910 variant enhances LPH promoter activity.7, 8 In our own experience, we did not observe a significant difference between subjects heterozygous for C/T-13910 and subjects with the lactase persistent homozygous genotype (T/T-13910) with respect to hydrogen production or clinical symptoms such as meteorism, flatulence, diarrhea, and cramping abdominal pain during a standard hydrogen breath test.9 We considered these patients to be lactose tolerant; therefore, we would not recommend avoiding lactose-containing products. In summary, all these data implicate that only patients with the C/C-13910 genotype (“lacking T”) suffer from lactose intolerance. Therefore, the observed decreased BMD and trend for increased risk for nonvertebral fractures in the women with the C/T-13910 genotype are difficult to understand.