Plastin 3基因多態(tài)性與絕經(jīng)后中國婦女骨密度及骨折的相關(guān)性研究
發(fā)布時(shí)間：2018-11-10 18:20
【摘要】：目的:Plastin 3(PLS3)基因位于X染色體上,編碼肌動(dòng)蛋白結(jié)合蛋白網(wǎng)素3(plastin3),該蛋白負(fù)責(zé)對(duì)肌動(dòng)蛋白細(xì)胞骨架的動(dòng)態(tài)裝配和拆卸。在鹿特丹研究(Rotterdam study)的人群中,PLS3基因突變被證實(shí)與骨質(zhì)疏松癥和骨折的發(fā)生有關(guān)。因此,本研究目的是探討PLS3基因的多態(tài)性是否與絕經(jīng)后中國女性的骨質(zhì)疏松性骨折的發(fā)生或低骨密度(BMD)風(fēng)險(xiǎn)相關(guān)。方法:共3661名無親緣關(guān)系的絕經(jīng)后婦女被招募,其中包括1083名骨質(zhì)疏松性骨折患者和2578名健康對(duì)照者。對(duì)所有參與者的PLS3基因的六個(gè)標(biāo)簽單核苷酸多態(tài)性(SNP)以及在鹿特丹研究中被確認(rèn)的與骨折相關(guān)的SNP(rs140121121)進(jìn)行基因分型。對(duì)其中的3166名受試者進(jìn)行了腰椎(L1-4),股骨頸和全髖骨密度的測(cè)定。結(jié)果:在3661名受試者中未發(fā)現(xiàn)rs140121121的多態(tài)性。此外,經(jīng)過Bonferroni校正,未發(fā)現(xiàn)PLS3基因的多態(tài)性與絕經(jīng)后中國婦女骨質(zhì)疏松性骨折或骨密度相關(guān)聯(lián)。結(jié)論:我們的研究結(jié)果表明,PLS3基因多態(tài)性與絕經(jīng)后中國女性骨質(zhì)疏松性骨折或低骨密度的風(fēng)險(xiǎn)無關(guān),可見PLS3基因在骨質(zhì)疏松性骨折及低骨密度風(fēng)險(xiǎn)方面所表現(xiàn)出來的遺傳影響在不同人種的人群中并不一致。目的:通過對(duì)2例低磷酸酶血癥(HPP)患者及家系進(jìn)行臨床分析和基因突變檢測(cè),拓展國人HPP的致病基因庫,并結(jié)合文獻(xiàn)探討HPP的致病機(jī)制。方法:對(duì)HPP家系中的先證者和其父母親進(jìn)行生化指標(biāo)檢測(cè)[血常規(guī)、肝腎功能、堿性磷酸酶(ALP)、甲狀旁腺素(PTH)、鈣、磷等]和骨密度檢測(cè)。同時(shí)對(duì)所有的研究對(duì)象進(jìn)行ALPL基因全部12個(gè)外顯子和外顯子內(nèi)含子交界區(qū)直接測(cè)序。結(jié)果:來自家系1的先證者為36歲成年男性,身高131.0cm,體重35.0kg。X線提示多發(fā)性胸腰椎骨折和骨盆畸形,生化檢測(cè)發(fā)現(xiàn)血清ALP 27U/L。測(cè)序發(fā)現(xiàn)ALPL基因6號(hào)外顯子532位雜合突變(c.532TC),導(dǎo)致ALPL成熟多肽中酪氨酸被組氨酸替代。該先證者的母親,身高140.5cm,體重39.5kg,血清ALP30U/L,基因測(cè)序證明其也是該雜合突變攜帶者。而來自家系2的先證者5歲,其外祖父母為近親結(jié)婚。該患兒身高100.0cm,體重18kg。血清ALP 55U/L[低于同年齡兒童(小于10歲)的正常值:75~344U/L],存在牙齒發(fā)育不良和脫落,有左股骨中下端骨折史。測(cè)序發(fā)現(xiàn)該患兒存在ALPL基因兩個(gè)錯(cuò)義突變,其中9號(hào)外顯子的c.871GA突變是Mornet在1998年報(bào)道的突變。而4號(hào)外顯子269位突變(c.269AG)是一個(gè)新的錯(cuò)義突變,該突變導(dǎo)致了成熟ALPL多肽中天冬氨酸被甘氨酸所替代。該患兒的母親亦是4號(hào)外顯子c.269AG錯(cuò)義突變的攜帶者,但是其生化指標(biāo)正常,無骨骼和牙齒的異常。結(jié)論:本研究發(fā)現(xiàn)的ALPL基因6號(hào)外顯子c.532TC突變和4號(hào)外顯子c.269AG突變是以往未曾報(bào)道過的新的錯(cuò)義突變,是上述兩例HPP患者的致病基因突變。
[Abstract]:Aim: Plastin 3 (PLS3) gene is located on X chromosome and encodes actin binding protein reticulin-3 (plastin3), which is responsible for the dynamic assembly and disassembly of actin cytoskeleton. In the Rotterdam study of (Rotterdam study), mutations in the PLS3 gene have been linked to osteoporosis and fracture. Therefore, the aim of this study was to investigate whether the polymorphism of PLS3 gene was associated with the occurrence of osteoporotic fracture or the risk of low bone mineral density (BMD) in postmenopausal Chinese women. Methods: a total of 3661 unrelated postmenopausal women were recruited, including 1083 patients with osteoporotic fractures and 2578 healthy controls. Six tagged single nucleotide polymorphisms (SNP) of the PLS3 gene and SNP (rs140121121) identified in the Rotterdam study were genotyped. 3166 of the subjects were measured for lumbar (L-1-4), femoral neck and total hip bone density. Results: no polymorphism of rs140121121 was found in 3661 subjects. In addition, no association between PLS3 gene polymorphism and osteoporosis fracture or bone mineral density in postmenopausal Chinese women was found after Bonferroni correction. Conclusion: our results suggest that PLS3 gene polymorphism is not associated with the risk of osteoporosis fracture or low bone density in postmenopausal Chinese women. The genetic effects of PLS3 gene on the risk of osteoporosis fracture and low bone mineral density were not consistent among different ethnic groups. Objective: to explore the pathogenetic gene pool of Chinese HPP by clinical analysis and gene mutation detection in 2 patients and families with hypophosphatase (HPP), and to explore the pathogenesis of HPP. Methods: the biochemical indexes (blood routine examination, liver and kidney function, alkaline phosphatase (ALP), parathyroid hormone (PTH), calcium, phosphorus, etc.) and bone mineral density (BMD) were measured in the probands and their parents of HPP families. All 12 exons and intron junctions of ALPL gene were sequenced. Results: the proband from pedigree 1 was a 36-year-old adult male with a height of 131.0 cm. The 35.0kg.X line indicated multiple thoracolumbar fractures and pelvic deformities. The serum ALP 27U / L was detected by biochemical examination. ALPL gene exon 6 was found to have a 532-position heterozygosity (c.532TC), which led to the replacement of tyrosine with histidine in mature ALPL polypeptides. The mother of the proband, who was 140.5 cm tall and 39.5 kg, was also found to be a carrier of the heterozygous mutation by serum ALP30U/L, gene sequencing. The proband, from family 2, was 5 years old, and his grandparents married close relatives. The child was 100.0 cm tall and weighed 18 kg. Serum ALP 55U/L [lower than the normal value of children of the same age (< 10 years old): 75~344U/L], dental dysplasia and exfoliation, history of fracture of left middle and lower femur. Two missense mutations in the ALPL gene were found in the patient by sequencing. The c.871GA mutation in exon 9 was reported by Mornet in 1998. Exon 4 (c.269AG) is a new missense mutation, which leads to the substitution of aspartic acid with glycine in mature ALPL polypeptides. The mother was also a carrier of c.269AG missense mutation in exon 4, but its biochemical parameters were normal and no abnormal bone and teeth were found. Conclusion: the c.532TC mutation in exon 6 of ALPL gene and the c.269AG mutation in exon 4 of ALPL gene are new missense mutations which have not been reported before. They are two pathogenetic gene mutations of HPP patients mentioned above.
【學(xué)位授予單位】：蘇州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R580
本文編號(hào)：2323241
[Abstract]:Aim: Plastin 3 (PLS3) gene is located on X chromosome and encodes actin binding protein reticulin-3 (plastin3), which is responsible for the dynamic assembly and disassembly of actin cytoskeleton. In the Rotterdam study of (Rotterdam study), mutations in the PLS3 gene have been linked to osteoporosis and fracture. Therefore, the aim of this study was to investigate whether the polymorphism of PLS3 gene was associated with the occurrence of osteoporotic fracture or the risk of low bone mineral density (BMD) in postmenopausal Chinese women. Methods: a total of 3661 unrelated postmenopausal women were recruited, including 1083 patients with osteoporotic fractures and 2578 healthy controls. Six tagged single nucleotide polymorphisms (SNP) of the PLS3 gene and SNP (rs140121121) identified in the Rotterdam study were genotyped. 3166 of the subjects were measured for lumbar (L-1-4), femoral neck and total hip bone density. Results: no polymorphism of rs140121121 was found in 3661 subjects. In addition, no association between PLS3 gene polymorphism and osteoporosis fracture or bone mineral density in postmenopausal Chinese women was found after Bonferroni correction. Conclusion: our results suggest that PLS3 gene polymorphism is not associated with the risk of osteoporosis fracture or low bone density in postmenopausal Chinese women. The genetic effects of PLS3 gene on the risk of osteoporosis fracture and low bone mineral density were not consistent among different ethnic groups. Objective: to explore the pathogenetic gene pool of Chinese HPP by clinical analysis and gene mutation detection in 2 patients and families with hypophosphatase (HPP), and to explore the pathogenesis of HPP. Methods: the biochemical indexes (blood routine examination, liver and kidney function, alkaline phosphatase (ALP), parathyroid hormone (PTH), calcium, phosphorus, etc.) and bone mineral density (BMD) were measured in the probands and their parents of HPP families. All 12 exons and intron junctions of ALPL gene were sequenced. Results: the proband from pedigree 1 was a 36-year-old adult male with a height of 131.0 cm. The 35.0kg.X line indicated multiple thoracolumbar fractures and pelvic deformities. The serum ALP 27U / L was detected by biochemical examination. ALPL gene exon 6 was found to have a 532-position heterozygosity (c.532TC), which led to the replacement of tyrosine with histidine in mature ALPL polypeptides. The mother of the proband, who was 140.5 cm tall and 39.5 kg, was also found to be a carrier of the heterozygous mutation by serum ALP30U/L, gene sequencing. The proband, from family 2, was 5 years old, and his grandparents married close relatives. The child was 100.0 cm tall and weighed 18 kg. Serum ALP 55U/L [lower than the normal value of children of the same age (< 10 years old): 75~344U/L], dental dysplasia and exfoliation, history of fracture of left middle and lower femur. Two missense mutations in the ALPL gene were found in the patient by sequencing. The c.871GA mutation in exon 9 was reported by Mornet in 1998. Exon 4 (c.269AG) is a new missense mutation, which leads to the substitution of aspartic acid with glycine in mature ALPL polypeptides. The mother was also a carrier of c.269AG missense mutation in exon 4, but its biochemical parameters were normal and no abnormal bone and teeth were found. Conclusion: the c.532TC mutation in exon 6 of ALPL gene and the c.269AG mutation in exon 4 of ALPL gene are new missense mutations which have not been reported before. They are two pathogenetic gene mutations of HPP patients mentioned above.
【學(xué)位授予單位】：蘇州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R580
【參考文獻(xiàn)】
相關(guān)期刊論文 前1條
1 王贖;劉建民;;骨質(zhì)疏松癥的全基因組關(guān)聯(lián)分析進(jìn)展[J];診斷學(xué)理論與實(shí)踐;2010年05期
，本文編號(hào)：2323241
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