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- van der Valk, Ralf J P, et al.
(författare)
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A novel common variant in DCST2 is associated with length in early life and height in adulthood.
- 2015
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 24:4, s. 1155-68
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Tidskriftsartikel (refereegranskat)abstract
- Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10(-4)) and adult height (N = 127 513; P = 1.45 × 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.
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- Erfurth, E M, et al.
(författare)
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Serum levels of insulin-like growth factor I and insulin-like growth factor-binding protein 1 correlate with serum free testosterone and sex hormone binding globulin levels in healthy young and middle-aged men
- 1996
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Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664. ; 44:6, s. 64-659
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Administration of testosterone has been reported to increase serum levels of IGF-I in men with isolated hypogonadotrophic hypogonadism. An inverse relation between serum IGF-I and sex hormone binding globulin (SHBG) is seen in GH deficient children. The biological action of IGF-I is thought to be influenced by binding proteins, one of which is insulin-like growth factor-binding protein-1 (IGFBP-1), which is not only a carrier protein but also actively regulates the cellular actions of IGF-I. These observations suggest associations between IGF-I, IGFBP-1, testosterone and SHBG in serum. The aim of the present study was to investigate these associations in normal healthy men.DESIGN AND PATIENTS: The associations between the serum levels of IGF-I and IGFBP-1 on one hand, and testosterone and SHBG on the other were investigated in 38 normal healthy young and middle-aged men.RESULTS: Serum levels of IGF-I decreased both with increasing age (r = -0.66, P < 0.001) and increasing SHBG levels (r = -0.46, P = 0.002), but increased with increasing free testosterone (f-testosterone) (r = 0.42, P = 0.005). These associations remained after mutual simultaneous adjustments in a multiple regression analysis. IGFBP-1 did not display any significant univariate correlation with age (r = -0.25, P = 0.06) or SHBG (r = 0.18, P = 0.14), but showed a significant positive correlation with both f-testosterone (r = 0.42, P = 0.004), and total testosterone (t-testosterone) (r = 0.39, P = 0.008). In a multiple regression analysis IGFBP-1 was positively correlated with both SHBG and f-testosterone, but not with t-testosterone.CONCLUSION: The present study suggests that among healthy young and middle-aged men, there is an association between serum levels of free-testosterone and SHBG on the one hand, and serum IGF-I and IGFBP-1 on the other.
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| 8. |
- Ahmad, T, et al.
(författare)
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Skeletal changes in type-2 diabetic Goto-Kakizaki rats.
- 2003
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Ingår i: The Journal of endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 178:1, s. 111-6
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Tidskriftsartikel (refereegranskat)abstract
- We characterized appendicular and axial bones in rats with type-2 diabetes in five female Goto-Kakizaki (GK) rats, a strain developed from the Wistar rat showing spontaneous type-2 diabetes, and five age- and sex-matched non-diabetic Wistar rats. The humerus, tibia, metatarsals and vertebral bodies were analysed by peripheral quantitative computerized tomography (pQCT). In diabetic rats, the height of the vertebral bodies and length of the humerus were decreased while the length of the metatarsals was increased. A decreased cross-sectional area was found in the vertebral end-plate region and the tibial metaphysis. Notably, the diaphysis in all long bones showed expansion of periosteal and endosteal circumference. In tibia this resulted in increased cortical thickness, whereas in humerus and metatarsal it was unchanged. Areal moment of inertia was increased in all diaphyses suggesting greater bending strength. The most conspicuous finding in diabetic rats pertained to trabecular osteopenia. Thus, trabecular bone mineral density was significantly reduced in all bones examined, by 33-53%. Our pQCT study of axial and appendicular bones suggests that the typical feature of diabetic osteopathy in the GK rat is loss of trabecular bone and expansion of the diaphysis. The loss of metaphyseal trabecular bone if also present in diabetic patients may prove to underlie the susceptibility to periarticular fracture and Charcot arthropathy. The findings suggest that the risk of fracture in diabetes varies according to the specific sub-regions of a bone. The approach described may prove to be useful in the early detection of osteopathy in diabetic patients who may be amenable to preventive treatment.
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