|
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.
Xiong DH, Xu FH, Liu PY, et al. Vitamin D receptor gene polymorphisms are linked to and associate with adult height. J Med Genet. 2005; 42:228-234.
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
|
Current GGH - Vol. 24 No. 1
Printer Friendly
Email Paper