The Journal of Clinical Endocrinology & Metabolism Vol. 84, No. 11 4293-4294
Copyright © 1999 by The Endocrine Society
No Association Was Found between Collagen 
I Type 1 Gene and Bone Density in Prepubertal Children
Chang Tao,
Sarah Garnett,
Vida Petrauskas and
Christopher T. Cowell
Robert Vines Growth Research Centre
New Children’s Hospital, Westmead 2145, Australia
Several candidate genes have been
identified that may influence bone mineral density (BMD) (1). Among
these candidate genes, polymorphism of the collagen 
I type 1
(CollA1) gene has been reported to cause differences in BMD in patients
with osteoporosis and in normal Caucasian population (2). Subsequently,
another study in 1778 Caucasian postmenopausal women showed that the
ColIA1 gene was related to decreased vertebral bone mass and vertebral
fractures (3). Therefore, it has been speculated that the ColIA1 gene,
as an osteoporosis candidate gene, mainly affects the rate of bone loss
in the aged population rather than attainment of peak bone mass. We
read with interest the study by Sainz et al. (4), which
reported that a polymorphism in the Sp1 binding site of the ColIA1 gene
affected cancellous volumetric BMD (vBMD) in prepubertal
Mexican-American girls. We report here our findings on the effect of
this polymorphism in the Sp1 binding site of the ColIA1 gene in
prepubertal boys and girls in a Caucasian population.
Two hundred fifty-eight healthy prepubertal Caucasian children (138
girls and 120 boys) in a narrow age range (7.0–8.9 years) participated
in a study, which had been approved by the New Children’s Hospital
Ethics committee. Bone density was measured by dual energy x-ray
absorptiometry using LUNAR DPX (LUNAR Radiation Corp., Madison, WI).
The v-BMD (g/cm3) was calculated from BMD at the femoral
neck (FN) and lumbar spine (LS), as described previously (5). The
effect of the genotypes on subject characteristics and bone density was
compared by analysis of variance. The distribution of genotypes of the
ColIA1 gene was compared between our data and that of Sainz et
al. (4) by Z-test on proportions. Significance levels were set at
less than 0.05. We found no association between the Sp1 genotypes of
the ColIA1 gene and vBMD at both LS and FN and (Table 1
).
However, we did find the distribution of Sp1 genotypes of the
ColIa1 gene in our Caucasian female population was different to that of
the female population from Mexican-American background (4) (see Table 2). No data were available for
Mexican-American males, and so they are not compared.
The haplotype ’S’ frequency was 0.81 in the female Caucasian
population and 0.89 in the female Mexican-American population. The
distribution of genotypes of ColIA1 gene in our study was similar to
the Caucasian female population (SS 67.1%, Ss 29.5% and ss 3.3%)
reported by Uitterlinden et al. (3).
The explanation for the difference on effect of the genotypes of
ColA1 gene in these two different ethnic prepubertal populations is not
clear. The higher frequency of ss genotype in the Caucasian groups
should theoretically have amplified the decrease in vBMD found by Sainz
et al. (4), but there was not even a trend by genotypes in
either sex, except at FN in the boys in our study. The smaller sample
size with ’S’ genotype in the study of Sainz et al. (4)
may have led to a selection bias. Alternatively, our study in using a
calculated vBMD from dual energy x-ray absorptiometry may have missed a
true difference in BMD when measured by quantitative computer
tomography in the study by Sainz et al. (4). It is also
possible that genotypes of the ColIA1 gene in different populations may
effect different outcomes on BMD. We conclude that our data do not
confirm that a polymorphism in the Sp1 binding site of the ColIa1 gene
affects vBMD of FN and LS in prepubertal Caucasian girls and boys.
Further studies taking account of the distribution of genotypes of
ColIA1 gene in different ethnic populations are required.
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