The relationship among serum insulin-like growth factor-I, insulin-like growth factor-I gene polymorphism, and bone mineral density in postmenopausal women in Korea

doi:10.1067/mob.2002.120483

American Journal of Obstetrics and Gynecology

Volume 186, Issue 3, March 2002, Pages 345-350

https://doi.org/10.1067/mob.2002.120483 Get rights and content

Abstract

OBJECTIVE: The objective of this study was to test the hypothesis that the cytosine-adenine polymorphism in the insulin-like growth factor-I gene is associated with serum insulin-like growth factor-I levels and bone mineral density. STUDY DESIGN: The insulin-like growth factor-I cytosine-adenine polymorphism was analyzed in 300 postmenopausal Korean women. Serum insulin-like growth factor-I, bone alkaline phosphatase, and carboxy-terminal cross-linking telopeptide of type I collagen were measured by immunoradiometric assay and enzyme-linked immunosorbent assay. Bone mineral density at the lumbar spine and proximal femur was determined by dual energy radiograph absorptiometry. RESULTS: Serum insulin-like growth factor-I and bone mineral density levels in women who were homozygous for a 194-base pair allele were significantly higher than those levels in the 194-base pair heterozygotes or women who did not possess the 194-base pair allele. A significantly decreased prevalence of the 194/194 genotype was observed in the combined group of women with osteopenia and osteoporosis, compared with normal women. No correlation between insulin-like growth factor-I genotypes and bone turnover markers was found. CONCLUSION: The insulin-like growth factor-I gene cytosine-adenine polymorphism relates with circulating insulin-like growth factor-I levels and bone mineral density at the lumbar spine and proximal femur. (Am J Obstet Gynecol 2002;186:345-50.)

Section snippets

Subjects

This study included 300 postmenopausal Korean women aged 45 to 75 years who visited the Menopause Clinic of Seoul National University Hospital for bone mass examination and who agreed to participate in the study. All subjects had been without spontaneous menses for at least 1 year and underwent a careful physical examination and a medical history review. Blood glucose and hepatic and renal function were determined. Women who had undergone bilateral oophorectomy or women with current hepatic or

Allele frequencies in a dinucleotide repeat of IGF-I gene

Table I shows the allele frequency distribution in a dinucleotide repeat of the IGF-I gene.

. The allele frequency distribution of IGF-I dinucleotide polymorphism

Fragment size(bp)	CA repeats(n)	Allele frequency
Fragment size(bp)	CA repeats(n)	n	%
176	12	1	0.2
180	13	1	0.2
182	14	8	1.3
184	15	25	4.2
186	16	109	18.2
188	17	157	26.2
190	18	93	15.5
192	19	86	14.3
194	20	119	19.8
196	21	1	0.2
TOTAL		600	100.0

Ten IGF-I alleles were observed, with product sizes that ranged between 176 bp (12 CA repeats) and 196 bp (21 CA repeats). Five major alleles with a frequency greater than 5%

Comment

Many genes that were believed to be involved in BMD have been investigated,2, 3 but osteoporosis genes have yet to be defined. Recently, our results have suggested that circulating IGF components play an important endocrinologic role in the maintenance of bone.⁵ The present cross-sectional study shows that the IGF-I gene CA polymorphism does not affect serum levels of biochemical markers of bone turnover and that this polymorphism is one of the genetic factors that may affect circulating IGF-I

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Although Cleveland et al. [12] have reported that women with the genotype lacking (CA) 19 repeat alleles have a significantly increased risk of breast cancer, the present study showed that the IGF-I (CA) repeat polymorphism was not related with endometriosis, an estrogen-dependent benign condition, as it is with breast cancer. Several studies were undertaken to evaluate the association between the IGF-I (CA) repeat polymorphism and circulating IGF-I levels, but the results have been conflicting, showing a decrease [15], an increase [16] and no change [17–19] in serum IGF-I levels among subjects carrying a (CA)19 repeat allele. As IGF levels were not measured in this study, whether circulating IGF levels are associated with the IGF-I polymorphism could not be confirmed.
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^☆: Supported by a grant of the Korea Health 21 Research and Development Project, Ministry of Health and Welfare, Republic of Korea (HMP-00-B-21000-0029).

^☆☆: Reprint requests: Jung Gu Kim, MD, PhD, Department of Obstetrics & Gynecology, Seoul National University Hospital, 28 Yeungun-dong Chongno-Ku, Seoul 110-744, Korea. E-mail: [email protected]

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General Obstetrics and Gynecology: GynecologyThe relationship among serum insulin-like growth factor-I, insulin-like growth factor-I gene polymorphism, and bone mineral density in postmenopausal women in Korea☆,☆☆

Abstract

Section snippets

Subjects

Allele frequencies in a dinucleotide repeat of IGF-I gene

Comment

Am J Obstet Gynecol

Bone

Bone

Bone

Environmental and genetic factors affecting bone mass. Similarity of bone density among members of healthy families

Arthritis Rheum

Recent progress in understanding the genetic susceptibility to osteoporosis

Genet Epidemiol

Role of genetic factors in the pathogenesis of osteoporosis

J Endocrinol

Skeletal growth factors and aging

J Clin Endocrinol Metab

The relationship among circulating insulin-like growth factor components, biochemical markers of bone turnover and bone mineral density in postmenopausal women under the age of 60

Clin Endocrinol

Genetic and environmental correlation among hormone levels and measures of body fat accumulation and topography

J Clin Endocrinol Metab

Abundant class of human DNA polymorphisms which can be typed using polymerase chain reaction

Am J Hum Genet

Association between serum insulin-like growth factor-I (IGF-I) and a simple sequence repeat in IGF-I gene: implications for genetic studies of bone mineral density

J Clin Endocrinol Metab

General Obstetrics and Gynecology: Gynecology
The relationship among serum insulin-like growth factor-I, insulin-like growth factor-I gene polymorphism, and bone mineral density in postmenopausal women in Korea☆,☆☆