长春市汉族女性维生素D受体基因Bsm Ⅰ和Fok Ⅰ位点多态性与骨密度相关性研究
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摘要
目的研究长春市35~85岁汉族女性维生素D受体(vitamin D receptor,VDR)基因Bsm Ⅰ、Fok Ⅰ位点的多态性,并分析其与骨密度(bone mineral density,BMD)的相关关系。方法采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术分析Bsm Ⅰ和Fok Ⅰ酶切位点多态性,采用Hologic Discovery WA型骨密度仪检测腰椎正位(L1~4)BMD。将230例受试者分成绝经组和未绝经组,观察两组各基因型分布特征,应用SPSS 19.0软件对试验结果进行统计分析。结果在本研究人群中,Bsm Ⅰ位点基因型分布情况为bb占83.9%、Bb占12.6%、BB占3.5%,b等位基因频率高达90.2%,B等位基因频率为9.8%;Fok Ⅰ位点基因型分布情况为ff占18.3%、Ff占43.9%、FF占37.8%,f等位基因频率为40.2%,F等位基因频率为59.8%,两位点基因型分布均符合Hardy-Weinberg定律(χ2=1.283,P=0.125;χ2=0.96,P=0.342);未绝经组与绝经组各基因型分布组间差异无统计学意义(P>0.05);Bsm Ⅰ位点在未绝经组和绝经组中各基因型BMD无差异(P>0.05);Fok Ⅰ位点ff型BMD较FF型和Ff型低,但在未绝经组中差异无统计学意义(P>0.05),绝经组中ff型与FF型比较,BMD差异有统计学意义(P<0.05)。结论在本研究的230例35~85岁汉族女性人群中,Bsm Ⅰ位点基因型分布以bb型为主,b等位基因频率高达90.2%,各基因型骨密度无差异;Fok Ⅰ位点ff型有较低的BMD,但在未绝经组中差异无统计学意义,在绝经后女性中ff型与低BMD相关。
Objective To study the polymorphisms of vitamin D receptor( VDR) gene Bsm Ⅰand Fok Ⅰin Han females aged 35-85 years in Changchun city and to analyze their relationship with bone mineral density. Methods Polymorphisms of Bsm Ⅰand Fok Ⅰwere analyzed by PCR-RFLP,and lumbar spine( L1-4) BMD were measured using Hologic Discovery-WA-type bone densitometer. 230 objects were grouped into postmenopausal group and premenopausal group,then we observed the distribution characteristics of each genotype. SPSS 19. 0 software was used to analyze the experimental result. Results In the present study,the genotype distributions of Bsm Ⅰwere bb( 83. 9%),Bb( 12. 6%) and BB( 3. 5%). The b allele frequency was as high as90. 2% and the B allele frequency was 9. 8%. The genotype distributions of Fok Ⅰwere ff( 18. 3%),Ff( 43. 9%) and FF( 37. 8%). The frequency of f allele was 40. 2% and the frequency of F allele was 59. 8%. The distribution of genotypes of both sites were in accordance with Hardy-Weinberg law( χ2 = 1. 283,P = 0. 125; χ2 = 0. 96,P = 0. 342). There was no significant difference in the genotype distribution between the premenopausal group and the postmenopausal group( P > 0. 05). In both premenopausal group and postmenopausal group,BMD for each genotype of Bsm Ⅰwas not significantly different( P > 0. 05).BMD of Fok Ⅰff type was lower than that of FF type and Ff type; BMD of these three genotypes was not significantly different in the premenopausal group( P > 0. 05),but BMD of ff type was lower than that of FF type in postmenopausal group( P < 0. 05).Conclusion In this study in 230 Han women aged 35 to 85 years,the distribution of Bsm Ⅰgenotype was mainly bb,the b allele frequency was as high as 90. 2%,and there was no significant difference in BMD between each genotype; Fok Ⅰff type had lower BMD,but there was no significant difference in the premenopausal group,and in postmenopausal women ff type was associated with lower BMD.
Objective To study the polymorphisms of vitamin D receptor( VDR) gene Bsm Ⅰand Fok Ⅰin Han females aged 35-85 years in Changchun city and to analyze their relationship with bone mineral density. Methods Polymorphisms of Bsm Ⅰand Fok Ⅰwere analyzed by PCR-RFLP,and lumbar spine( L1-4) BMD were measured using Hologic Discovery-WA-type bone densitometer. 230 objects were grouped into postmenopausal group and premenopausal group,then we observed the distribution characteristics of each genotype. SPSS 19. 0 software was used to analyze the experimental result. Results In the present study,the genotype distributions of Bsm Ⅰwere bb( 83. 9%),Bb( 12. 6%) and BB( 3. 5%). The b allele frequency was as high as90. 2% and the B allele frequency was 9. 8%. The genotype distributions of Fok Ⅰwere ff( 18. 3%),Ff( 43. 9%) and FF( 37. 8%). The frequency of f allele was 40. 2% and the frequency of F allele was 59. 8%. The distribution of genotypes of both sites were in accordance with Hardy-Weinberg law( χ2 = 1. 283,P = 0. 125; χ2 = 0. 96,P = 0. 342). There was no significant difference in the genotype distribution between the premenopausal group and the postmenopausal group( P > 0. 05). In both premenopausal group and postmenopausal group,BMD for each genotype of Bsm Ⅰwas not significantly different( P > 0. 05).BMD of Fok Ⅰff type was lower than that of FF type and Ff type; BMD of these three genotypes was not significantly different in the premenopausal group( P > 0. 05),but BMD of ff type was lower than that of FF type in postmenopausal group( P < 0. 05).Conclusion In this study in 230 Han women aged 35 to 85 years,the distribution of Bsm Ⅰgenotype was mainly bb,the b allele frequency was as high as 90. 2%,and there was no significant difference in BMD between each genotype; Fok Ⅰff type had lower BMD,but there was no significant difference in the premenopausal group,and in postmenopausal women ff type was associated with lower BMD.
引文
[1]崔健,陈虹,黄秉仁,等.维生素D受体最新研究进展.生理科学进展,2011,42(2):95-99.Cui J,Chen H,Huang BR,et al.The recent progress in the studies of vitam in D receptor.Prog Physiol Sci,2011,42(2):95-99.(in Chinese)
[2]Morrison NA,Qi JC,Tokita A,et al.Prediction of bone density from vitamin D receptor alleles.Nature,1994,367(6460):284-287.
[3]李富林,黄宇,尹东,等.骨质疏松症与维生素D受体基因Fok I Bsm I Apa I Taq I多态性的研究进展.中国临床新医学,2015,8(9):894-896.Li FL,Huang Y,Yin D,et al.Advances in the study of vitamin D receptor gene Fok I,Bsm I,Apa I,Taq I polymorphism and osteoporosis.Chin J New Clin Med,2015,8(9):894-896.(in Chinese)
[4]Zmuda JM,Sheu YT,Moffett SP.The search for human osteoporosis genes.J Musculoskelet Neuronal Interact,2006,6(1):3-15.
[5]李兴勇,徐霞,姚兴璋,等.维生素D受体多态性位点与骨疾病发病的相关性.中国中医骨伤科杂志,2013,21(6):70-72.Li XY,Xu X,Yao XZ,et al.Relationship between vitamin D receptor polymorphism and pathogenesis of bone diseases.Chin J Tradit Med Traumatol Orthop,2013,21(6):70-72.(in Chinese)
[6]Saadi A,Gao G,Li H,et al.Association study between vitamin D receptor gene poly morphisms and asthma in the Chinese Han population:Acase-control study.BMC Med Genet,2009,21(5):10-71.
[7]王秀玲,朱秀英,聂英昆,等.哈尔滨地区部分汉族人群维生素D受体BsmⅠ基因多态性与骨质疏松性骨折关系的研究.中国骨质疏松杂志,2007,13(10):692-695.Wang XL,Zhu XY,Nie YK,et al.Analysis of relationship between vitamin D receptor gene BsmⅠpolymorphism and osteoporotic fracture in part of the Han population in Harbin.Chin J Osteopor,2007,13(10):692-695.(in Chinese)
[8]Zhang HH,Tao GS,Wu Q,et al.Studies on the frequencies of vitamin D receptorgene polymorphism in postmenopausalwomen lf Gan and Kazak nationality in China.J Bone Metab,2001,19(5):321-323.
[9]Ukaji M,Saito Y,Fukushima-Uesaka H,et al.Genetic variations of VDR/NR I II encoding vitamin D receptor in a Japanese population.Drug Metab Pharmacokinet,2007,22(6):462-467.
[10]Kim JG,Kwon JH,Kim SH,et al.Association between vitamin dreceptor gene haplotypes and bone mass in postmenopausal Korean women.Am J Obstet Gynecol,2003,189(5):1234-1240.
[11]缪应新,朱汉民,朱晓颖,等.611例汉族人维生素D受体基因多态性与骨密度关系研究.中华内分泌代谢杂志,2005,21(5):448-449.Miao YX,Zhu HM,Zhu XY,et al.Relationship between bonemineral density and polymorphism of vitamin D receptor gene in 611 Hans.Chin J Endocrinol Metab,2005,21(5):448-449.(in Chinese)
[12]吴文,智喜梅,李东风,等.广州地区绝经后妇女维生素D受体基因多态性与骨密度关系的研究.中国病理生理杂志,2007,23(3):563-565.Wu W,Zhi XM,Li DF,et al.Relationship between bonem ineral density and polymorphism of vitam in D receptor gene in postmenopausalwomen in Guangzhou.Chin J Pathophys,2007,23(3):563-565.(in Chinese)
[13]吴文,智喜梅,李东风,等.广州地区绝经前妇女维生素D受体基因多态性与骨密度无关.南方医科大学学报,2007,27(3):364-366.Wu W,Zhi XM,Li DF,et al.Vitamin D receptor gene polymorphism is not associated with bone mineral density of premenopausal women in Guangzhou.J South Med Univ,2007,27(3):364-366.(in Chinese)
[14]韩昕,詹志伟,张红红,等.北京部分汉族男性维生素D受体基因FokⅠ多态性与骨密度的关系.中国组织工程研究与临床康复,2009,13(24):4763-4766.Han X,Zhan ZW,Zhang HH,et al.Association between vitamin D receptor genetypes of FokⅠpolymorphism and bone mineral density in male of the Han nationality in Beijing area.Chinese Journal of Tissue Engineering Research,2009,13(24):4763-4766.(in Chinese)
[15]Morita A,Iki M,Dohi Y,et al.Prediction of bone mineral density from vitamin D receptor polymorphisms is uncertain in representative samples of Japanese women.The Japanese Population-based Osteoporosis(JPOS)Study.Int J Epidemiol,2004,33(5):979-988.
[16]Yasovanthi J,Venkata Karunakar K,Sri Manjari K,et al.Associationof vitamin D receptor gene polymorphisms with BMD and their effect on 1,25-dihydroxy vitamin D3 levels in pre-and postmenopausal South Indian women from Andhra Pradesh.Clin Chim Acta,2011,412(7-8):541-544.
[17]Kalak R,Marcinkowska M,Slomski R.Association analysis of the polymorphisms of the VDR gene with bone mineral density and the occurrence of fractures.J Bone Miner Metab,2007,25(5):310-319.
[18]章振林,何进卫,黄琪仁,等.维生素D受体基因起始密码子和CDX2多态性与钙剂补充对绝经后妇女骨密度作用的关系.中华医学遗传学杂志,2006,23(4):397-401.Zhang ZL,He JW,Huang QR,et al.Association of polymorphisms of vitamin D receptor gene start codon and 3-end region with bone mineral density in postmenopausl women.Chin J Med Genet,2006,23(4):397-401.(in Chinese)
[2]Morrison NA,Qi JC,Tokita A,et al.Prediction of bone density from vitamin D receptor alleles.Nature,1994,367(6460):284-287.
[3]李富林,黄宇,尹东,等.骨质疏松症与维生素D受体基因Fok I Bsm I Apa I Taq I多态性的研究进展.中国临床新医学,2015,8(9):894-896.Li FL,Huang Y,Yin D,et al.Advances in the study of vitamin D receptor gene Fok I,Bsm I,Apa I,Taq I polymorphism and osteoporosis.Chin J New Clin Med,2015,8(9):894-896.(in Chinese)
[4]Zmuda JM,Sheu YT,Moffett SP.The search for human osteoporosis genes.J Musculoskelet Neuronal Interact,2006,6(1):3-15.
[5]李兴勇,徐霞,姚兴璋,等.维生素D受体多态性位点与骨疾病发病的相关性.中国中医骨伤科杂志,2013,21(6):70-72.Li XY,Xu X,Yao XZ,et al.Relationship between vitamin D receptor polymorphism and pathogenesis of bone diseases.Chin J Tradit Med Traumatol Orthop,2013,21(6):70-72.(in Chinese)
[6]Saadi A,Gao G,Li H,et al.Association study between vitamin D receptor gene poly morphisms and asthma in the Chinese Han population:Acase-control study.BMC Med Genet,2009,21(5):10-71.
[7]王秀玲,朱秀英,聂英昆,等.哈尔滨地区部分汉族人群维生素D受体BsmⅠ基因多态性与骨质疏松性骨折关系的研究.中国骨质疏松杂志,2007,13(10):692-695.Wang XL,Zhu XY,Nie YK,et al.Analysis of relationship between vitamin D receptor gene BsmⅠpolymorphism and osteoporotic fracture in part of the Han population in Harbin.Chin J Osteopor,2007,13(10):692-695.(in Chinese)
[8]Zhang HH,Tao GS,Wu Q,et al.Studies on the frequencies of vitamin D receptorgene polymorphism in postmenopausalwomen lf Gan and Kazak nationality in China.J Bone Metab,2001,19(5):321-323.
[9]Ukaji M,Saito Y,Fukushima-Uesaka H,et al.Genetic variations of VDR/NR I II encoding vitamin D receptor in a Japanese population.Drug Metab Pharmacokinet,2007,22(6):462-467.
[10]Kim JG,Kwon JH,Kim SH,et al.Association between vitamin dreceptor gene haplotypes and bone mass in postmenopausal Korean women.Am J Obstet Gynecol,2003,189(5):1234-1240.
[11]缪应新,朱汉民,朱晓颖,等.611例汉族人维生素D受体基因多态性与骨密度关系研究.中华内分泌代谢杂志,2005,21(5):448-449.Miao YX,Zhu HM,Zhu XY,et al.Relationship between bonemineral density and polymorphism of vitamin D receptor gene in 611 Hans.Chin J Endocrinol Metab,2005,21(5):448-449.(in Chinese)
[12]吴文,智喜梅,李东风,等.广州地区绝经后妇女维生素D受体基因多态性与骨密度关系的研究.中国病理生理杂志,2007,23(3):563-565.Wu W,Zhi XM,Li DF,et al.Relationship between bonem ineral density and polymorphism of vitam in D receptor gene in postmenopausalwomen in Guangzhou.Chin J Pathophys,2007,23(3):563-565.(in Chinese)
[13]吴文,智喜梅,李东风,等.广州地区绝经前妇女维生素D受体基因多态性与骨密度无关.南方医科大学学报,2007,27(3):364-366.Wu W,Zhi XM,Li DF,et al.Vitamin D receptor gene polymorphism is not associated with bone mineral density of premenopausal women in Guangzhou.J South Med Univ,2007,27(3):364-366.(in Chinese)
[14]韩昕,詹志伟,张红红,等.北京部分汉族男性维生素D受体基因FokⅠ多态性与骨密度的关系.中国组织工程研究与临床康复,2009,13(24):4763-4766.Han X,Zhan ZW,Zhang HH,et al.Association between vitamin D receptor genetypes of FokⅠpolymorphism and bone mineral density in male of the Han nationality in Beijing area.Chinese Journal of Tissue Engineering Research,2009,13(24):4763-4766.(in Chinese)
[15]Morita A,Iki M,Dohi Y,et al.Prediction of bone mineral density from vitamin D receptor polymorphisms is uncertain in representative samples of Japanese women.The Japanese Population-based Osteoporosis(JPOS)Study.Int J Epidemiol,2004,33(5):979-988.
[16]Yasovanthi J,Venkata Karunakar K,Sri Manjari K,et al.Associationof vitamin D receptor gene polymorphisms with BMD and their effect on 1,25-dihydroxy vitamin D3 levels in pre-and postmenopausal South Indian women from Andhra Pradesh.Clin Chim Acta,2011,412(7-8):541-544.
[17]Kalak R,Marcinkowska M,Slomski R.Association analysis of the polymorphisms of the VDR gene with bone mineral density and the occurrence of fractures.J Bone Miner Metab,2007,25(5):310-319.
[18]章振林,何进卫,黄琪仁,等.维生素D受体基因起始密码子和CDX2多态性与钙剂补充对绝经后妇女骨密度作用的关系.中华医学遗传学杂志,2006,23(4):397-401.Zhang ZL,He JW,Huang QR,et al.Association of polymorphisms of vitamin D receptor gene start codon and 3-end region with bone mineral density in postmenopausl women.Chin J Med Genet,2006,23(4):397-401.(in Chinese)