Ho, AYY

Kung, AWC

Lau, HL

Luk, KDK

Hong Kong Medical Journal

Genetic contributions play an important role in determining bone mineral density (BMD) and bone turnover. Transforming growth factor-β (TGF-β) is abundant in bone and has been implicated as an important regulator of both bone formation and resorption. Several polymorphisms of the TGF-β1 gene have recently been suggested to be associated with BMD and susceptibility to osteoporotic spine fractures. To determine the relationship between TGF-β1 polymorphisms and BMD in southern Chinese women, three SNPs at C -1348-T, T29-C, and T861-20-C of TGF-β1 gene were analyzed in 237 postmenopausal southern Chinese women by RFLP and direct sequencing. BMD at the lumbar spine and hip region, biochemical markers of bone turnover, as well as serum levels of TGF-β1 were measured. Only the T29-C polymorphism of TGF-β1 gene was associated with BMD and fracture risk. The prevalence of fragility fractures was significantly higher in individuals with TC genotype (P < 0.05). Serum alkaline phosphatase and osteocalcin levels as well as urinary N-telopeptide excretion were significantly higher in women with TC than with TT or CC genotypes, and the difference remained significant after adjusting for age and BMI (all P < 0.05). Women with TC genotype had lower BMD at the trochanteric (P < 0.03) and total hip region (P = 0.05). No difference was observed in the serum TGF-β1 levels among the three genotypes. In conclusion, an association between T 29-C polymorphisms of TGF-β1 gene and BMD, bone turnover as well as fragility fractures were demonstrated in postmenopausal southern Chinese women.link_to_subscribed_fulltex

Lau, HHL

HKU Scholars Hub

Calcified Tissue International

Transforming growth factor-β1 gene polymorphisms and bone turnover, bone mineral density and fracture risk in southern Chinese women

TitleTransforming growth factor-betal gene polymorphisms and boneturnover, bone mineral density and fracture risk in southernChinese womenAuthor(s) Lau, HL; Ho, AYY; Luk, KDK; Kung, AWCCitationThe 8th Medical Research Conference Abstracts, Hong KongMedical Journal, Hong Kong, China, 25-26 January 2003, v. 9 n. 1Supp 1, p. 32Issued Date 2003URL http://hdl.handle.net/10722/46899Rights Creative Commons: Attribution 3.0 Hong Kong License32      HKMJ Vol 9 No 1 February 2003 SupplementDevelopment of a murine model of autoimmune thyroiditis induced with homologousmouse thyroid perioxidaseHP Ng, Annie WC Kung. Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong,Autoimmune Thyroid Disease (AITD) is a common condition affecting mostly female subjects. Thyroid peroxi-dase (TPO) is a well-characterized autoantigen in AITD. Autoantibodies and autoreactive T lymphocytes to TPOare believed to play a major role in the pathogenesis of lymphocytic thyroiditis. To understand the pathogenicmechanisms of AITD and the role of TPO, we have established a mouse model of lymphocytic thyroiditis byimmunizing C57Bl/6(H-2b), CBA (H-2k) and C57Bl/6 × CBA F1 mice with recombinant mTPO (rmTPO) ectodomaincomprising amino acid residue 1-837 produced in E.coli. Mice were immunized with 30mg purified ectodomain incomplete Freund’s adjuvant. Antibodies against rmTPO were detected in the serum of all mice from week 3 onwards.Draining lymph node cells from rmTPO-immunized animals showed dose dependent proliferation to TPO stimulation.Mice sacrificed at day 50 revealed variable degree of thyroiditis with infiltration of mononuclear cells and destruc-tion of thyroid follicles. C57Bl/6 and the F1 mice, in comparison to CBA mice, showed greater degree of thyroiditisand subnormal serum T4 levels. The degree of histological features of thyroiditis corresponded to the biochemicalabnormalities of these animals but not to the anti-TPO antibody response. Immunotyping of the thyroid cellularinfiltrates showed predominantly CD4+ T cells and B220+ B cells but scanty CD8+ T cells. None of the controlmice injected with the purified fusion partner developed anti-TPO antibodies and thyroiditis. Significant weightgain was exhibited in the mTPO-immunized animals, with the degree of hypothyroidism correlated strongly withthe amount of weight gain, giving additional supportive evidence of thyroid dysfunction. In conclusion, a genuinemouse model of AITD induced with rmTPO was established which possessed all features of lymphocytic thyroiditis.This model will enable the study and understanding of the autoimmune process of AITD and may assist in thedevelopment of new strategies for modulating the pathogenic immune response involved in this disease.Transforming growth factor-beta1 gene polymorphisms and bone turnover, bonemineral density and fracture risk in southern Chinese womenLau HHL1, Ho AYY1, Luk KDK2 and Kung AWC1. Departments of Medicine1 & Orthopaedic Surgery2, The University ofHong Kong, Queen Mary Hospital, Hong KongGenetic contributions play an important role in determining bone mineral density (BMD) and bone turnover. Trans-forming growth factor-beta (TGF-beta) is abundant in bone and has been implicated as an important regulator ofboth bone formation and resorption. A T→C polymorphism in exon 1 of the TGF-beta1 gene, which results in thesubstitution of proline for leucine, has recently been suggested to be associated with higher BMD. In the presentstudy, we analyzed the relationship between TGF-beta1 polymorphism and BMD in southern Chinese women. TheTC polymorphic site of TGF-beta1 gene at nucleotide position 29 was analyzed in 366 healthy southern Chinesewomen by direct sequencing. BMD at lumbar spine and hip region, biochemical markers of bone turnover and PTHlevel were measured. Among the postmenopausal women (n=239), the prevalence of fragility fractures was signifi-cantly higher in individuals with TC genotype (p<0.05). Serum alkaline phosphatase and osteocalcin as well asurine N-telopeptide excretion were significantly higher in women with TC than TT or CC genotypes (all p<0.05).Women with TC genotype had lower BMD at total hip, femoral neck and trochanteric region. However, afteradjusting for age, height, weight and years since menopause, the BMD at both the hip and spine did not differamong the three genotypes. With respect to the premenopausal women (n=127), no difference was seen in the BMDat the hip or spine among the three groups. In conclusion, we observed an association between TGF-beta1 genepolymorphism and bone turnover as well as fragility fractures in postmenopausal southern Chinese women.EM-03EM-04

Transforming growth factor-betal gene polymorphisms and bone turnover, bone mineral density and fracture risk in Southern Chinese Women

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Transforming growth factor-betal gene polymorphisms and bone turnover, bone mineral density and fracture risk in Southern Chinese Women

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