Vitamin D Receptor and Adult Height
© 2005 Prime Health Consultants, Inc.
Height in “normal” individuals is a complex trait known to be influenced by nutrition, environment, and especially genetics. Several chromosomal regions and even genes have been identified in genome-wide screening studies to influence variability in height. One of the genes encodes the vitamin D receptor (VDR), which is not surprising given its functions in metabolic pathways and calcium and phosphorous homeostasis. The investigation reported by Xiong et al sheds further light on the subject.
The authors used a method termed the quantitative transmission disequilibrium test (QTDT) to search for linkage and/or association of 4 highly polymorphic single nucleotide polymorphisms (SNPs) in the VDR gene with height in a large sample of 1873 white subjects of European origin from 406 nuclear families. All individuals were 19 years old or older and had or nearly reached their adult heights. After adjusting for age, sex, and menopausal status (for females) the heights of the individuals showed a normal distribution. The SNPs spanned the 9-exon gene: 2 mapping to the 5’ end of the gene and 2 mapping to near the 3’ untranslated end of the gene.
Analysis of the data showed first that heritability of height in this group was 78% indicating a large influence of genetic factors as expected. All 4 SNPs displayed linkage of adult height variation to the VDR locus. Among the 4 SNPs tested, the 2 nearest the 3’ untranslated region of the gene showed the greatest influence on height. For example, individuals carrying a G base at one of the positions and T base at the other were taller than individuals carrying an A base and a C base at the same positions. The reasons why these differences affect height are not known. However, interestingly, the association of one of the patterns with height was most significant for pre- and perimenopausal women and not significant for men or postmenopausal women, raising the possibility that that the genetic effect involves “height retention” after menopause.
Editor’s Comment: The paper shows that linkage analysis can still provide clues as to how genetic variation influences quantitative traits such as height, even if we don’t understand the underlying mechanism(s).
William A. Horton, MD