Genetic Components of Lactose Intolerance and Community Frequency

Abstract

The fact that individuals heterozygous for primary adult lactose intolerance (LCT -13910 ) show intermediate BMDs is indeed interesting, and on this point, we fully agree with Büning et al. In our results, we explicitly mentioned an "increasing, but not significant gene-dose effect" in nonvertebral fractures and low BMD for heterozygous subjects.(1)In fact, it has recently been shown that subjects heterozygous for the LCT -13910 polymorphism have reduced lactase activity (2) compared with homozygous lactose-tolerant subjects. However, the ratio of lactase/sucrase activity in this study was significantly higher in LCT -13910 heterozygous subjects than in homozygous lactose-intolerant individuals. This remaining activity is possibly sufficient for clinically unremarkable lactose maldigestion, but nonetheless, may exert effects on bone metabolism and osteoporosis risk over a longer period. The observation of decreased BMD in LCT -13910 heterozygous subjects, therefore, rather additionally supports than contradicts our conclusion that adult-type hypolactasia is associated with osteoporosis.The aversion to dairy nutrients and a consequently decreased calcium supply together with intestinal calcium malabsorption may well be the first and most important cause of an individually decreased calcium balance and risk for osteoporosis in lactose-intolerant subjects. However, we have increasing evidence that some of the effects of the LCT -13910 polymorphisms on bone size and stature might not be calcium dependent alone, because they persist after correction for calciotropic parameters (JBJ van Meurs and AG Uitterlinden, personal communication, 2004).(3) Thus, some of the regulatory aspects of the lactase phlorizin hydrolase (LPH) gene have to be assumed to be independent of a simple lactose intolerance effect per se.Furthermore, we have to consider several other environmental and genetic influences on calcium and lactose digestion that interfere with the LPH conditions, such as the vitamin D system. Our and other recent data show a strong influence of the vitamin D system on the severity and phenotypical consequence of lactose intolerance regarding bone, (3) which will be further analyzed.We have to state clearly that primary adult lactose intolerance is a condition that affects about one-half of the world's population. It has a severe impact on calcium supply and bone properties and should be kept in mind in every future human nutritional and pharmaceutical study in this field. The new possibility of an exact diagnostic tool for lactose intolerance using LCT -13910 genotyping will add further aspects to the discussion on consumption of dairy nutrients that is ongoing in the Journal, (4) because the intake of diary nutrients is directly influenced by the genetic disposition to lactose intolerance, at least in adults.Further investigations, including interventional studies, will be necessary to fully explain the role of lactase activity and lactose intolerance for osteoporosis.

Analysis of LCT-13910 genotypes and bone mineral density in ancient skeletal materials

“…We noted higher, but not statistically significant frequency of OP in LI group ( p = 0.60). Although there are no ancient comparative data on BMD and LCT-13910 genotypes, our data are consistent with previously reported results acquired for radius, total hip and the Ward’s triangle BMD in a present-day postmenopausal Caucasian women [ 6 ] or for lumbar and femoral neck BMD in a postmenopausal women from Austria [ 5 ]. The association of lower BMD and LCT-13910 CC genotype has been also indicated in the studies of elderly people [ 29 ] and recently in the modern children from Malay in Malesia [ 30 ].…”

“…In Europe the LT has increased from Iron Age through Medieval Period till present day times [ 12 ]. Nowadays the frequency of LI in Europe, represented by LCT-13910 CC genotypes, varies from 2% in Scandinavia to 20–40% in Central Europe [ 5 ] and to 60–70% in Italy and Turkey [ 13 ].…”