Linkage map of the short arm of human chromosome 11: location of the genes for catalase, calcitonin, and insulin-like growth factor II.

Kittur, Smita; Höppener, Jo W.M.; Antonarakis, Stylianos E.; Daniels, Jane D. J.; Meyers, Deborah A.; Maestri, Nancy E.; Jansen, M.; Korneluk, Robert G.; Nelkin, Barry D.; Kazazian, Haig H.

doi:10.1073/pnas.82.15.5064

Cited by 78 publications

(25 citation statements)

References 40 publications

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“…Current data indicate that a single gene for IGF-II is located on chromosome 11 (19,20) adjacent to the insulin gene (21,22). However, the 5' untranslated region of the human cDNA clones is different from the 5' sequence reported in the genomic clone (23 …”

Section: Ipmentioning

confidence: 85%

Tissue-specific expression of insulin-like growth factor II mRNAs with distinct 5' untranslated regions.

Irminger¹,

Rosen²,

Humbel³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

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We have used RNA from human hypothalamus as template for the production of cDNAs encoding insulin-like growth factor II (IGF-II). The prohormone coding sequence of brain IGF-II RNA is identical to that found in liver; however, the 5' untranslated sequence of the brain cDNA has no homology to the 5' untranslated sequence of the previously reported liver cDNAs. By using hybridization to specific probes as well as a method based on the properties of RNase H, we found that the human IGF-II gene has at least three exons that encode alternative 5' untranslated regions and that are expressed in a tissue-specific manner. A probe specific to the brain cDNA 5' untranslated region hybridizes to a 6.0-kilobase transcript present in placenta, hypothalamus, adrenal gland, kidney, Wilms tumor, and a pheochromocytoma. The 5' untranslated sequence of the brain cDNA does not hybridize to a 5.3-kilobase transcript found in liver or to a 5.0-kb transcript found in pheochromocytoma. By using RNase H to specifically fragment the IGF-II transcripts into 3' and 5' fragments, we found that the RNAs vary in size due to differences in the 5' end but not the 3' end.

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Section: Ipmentioning

confidence: 85%

Tissue-specific expression of insulin-like growth factor II mRNAs with distinct 5' untranslated regions.

Irminger¹,

Rosen²,

Humbel³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

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“…CGRP has been reported to recruit macrophages into osteoclast-like cells (Owan and Ibaraki 1994), to inhibit bone resorption (Roos et al 1986), and to stimulate osteogenesis (Bernard and Shih 1990). It is possible that the allelic genotype associated with the lower BMD in our test subjects may be in linkage disequilibrium with a mutation in CGRP; another possibility is involvement of the gene encoding PTH, which lies in the same genomic vicinity as CT (Kittur et al 1985). This spatial relationship is intriguing when we consider the importance of both hormones in calcium metabolism.…”

Section: Discussionmentioning

confidence: 89%

Association of bone mineral density with a dinucleotide repeat polymorphism at the calcitonin (CT) locus

et al. 2000

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Calcitonin (CT), a calcium-regulating hormone, lowers the calcium level in serum by inhibiting bone resorption. Because CT may play a role in the pathogenesis of osteoporosis, genetic variations in or adjacent to the CT gene may be associated with variations in bone mineral density (BMD). The present study examined the correlation between a dinucleotide (cytosine-adenine; CA) repeat polymorphism at the CT locus and BMD in 311 Japanese postmenopausal women (mean age, 64.1 years). Seven alleles were present in this population; each allele contained 10, 11, 16, 17, 18, 19, or 20 CA repeats. Thus, we designated the respective genotypes A10, A11, A16, A17, A18, A19, and A20. The A10 and A17 alleles were the predominant alleles in the population studied. Z scores (a parameter representing deviation from the age-specific weight-adjusted average BMD) were compared between individuals that possessed one or two alleles of each genotype and those that did not possess the allele. Subjects who possessed one or two A10 alleles had lower BMD Z scores than those who did not (lumbar 2-4 BMD Z score; Ϫ0.148 Ϯ 1.23 vs 0.182 Ϯ 1.54; P ϭ 0.04). No significant relationships were observed between allelic status and background data or biochemical parameters. The significant association observed between BMD and genetic variations at the CT locus implies that polymorphism at this locus may be a useful marker for the genetic study of osteoporosis.

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“…(1) It has long been used as a therapeutic agent because of its antiresorptive properties, effected by binding to specific G protein-coupled receptors on osteoclasts. (2) Pharmaceutical preparations of calcitonin generally use salmon calcitonin (sCT) because it is a more potent antiresorptive than human calcitonin. (3) Synthetic salmon calcitonin (ssCT), administered parenterally, is used for treatment of Paget's disease, hypercalcemia, and osteoporosis.…”

Section: Introductionmentioning

confidence: 99%

A phase 3 trial of the efficacy and safety of oral recombinant calcitonin: The oral calcitonin in postmenopausal osteoporosis (ORACAL) trial

Binkley

Bolognese²,

Sidorowicz-Bialynicka³

et al. 2012

Journal of Bone and Mineral Research

131

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The Oral Calcitonin in Postmenopausal Osteoporosis (ORACAL) study was a randomized, double-blind, double-dummy, active-and placebo-controlled, multiple-dose, phase 3 study to assess the efficacy and safety of oral recombinant calcitonin for treatment of postmenopausal osteoporosis. A total of 565 women age 46 to 86 (mean 66.5) years were randomized (4:3:2) to receive oral recombinant salmon calcitonin (rsCT) tablets (0.2 mg/d) plus placebo nasal spray, synthetic salmon calcitonin (ssCT) nasal spray (200 IU/d) plus placebo tablets, or placebo (placebo tablets plus placebo nasal spray), respectively for 48 weeks. All women received calcium (!1000 mg/d) and vitamin D (800 IU/d). Women randomized to oral rsCT had a mean AE SD percent increase from baseline in lumbar spine bone mineral density (BMD) (1.5% AE 3.2%) that was greater than those randomized to ssCT nasal spray (0.78% AE 2.9%) or placebo (0.5% AE 3.2%). Lumbar spine BMD change in those receiving nasal calcitonin did not differ from placebo. Oral rsCT treatment also resulted in greater improvements in trochanteric and total proximal femur BMD than ssCT nasal spray. Reductions in bone resorption markers with oral rsCT were greater than those observed in ssCT nasal spray or placebo recipients. Approximately 80% of subjects in each treatment group experienced an adverse event, the majority of which were mild or moderate in intensity. Gastrointestinal system adverse events were reported by nearly one-half of women in all treatment groups and were the principal reason for premature withdrawals. Less than 10% of women experienced a serious adverse event and no deaths occurred. Overall, oral rsCT was superior to nasal ssCT and placebo for increasing BMD and reducing bone turnover. Oral rsCT was safe and as well tolerated as ssCT nasal spray or placebo. Oral calcitonin may provide an additional treatment alternative for women with postmenopausal osteoporosis. ß

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Linkage map of the short arm of human chromosome 11: location of the genes for catalase, calcitonin, and insulin-like growth factor II.

Cited by 78 publications

References 40 publications

Tissue-specific expression of insulin-like growth factor II mRNAs with distinct 5' untranslated regions.

Tissue-specific expression of insulin-like growth factor II mRNAs with distinct 5' untranslated regions.

Association of bone mineral density with a dinucleotide repeat polymorphism at the calcitonin (CT) locus

A phase 3 trial of the efficacy and safety of oral recombinant calcitonin: The oral calcitonin in postmenopausal osteoporosis (ORACAL) trial

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