The correlation of gene polymorphisms andTaiwanese osteonecrosis patients with SLE

• Main Authors: Wan-Ting Huang, 黃琬婷
• Other Authors: Gwo-Jaw Wang
• Format: Others
• Language: zh-TW
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/69177066881174756993

碩士 === 高雄醫學大學 === 醫學研究所 === 96 === Osteonecrosis (ON), also called the avascular necrosis (AVN), is a disease that leads to eventual bone collapse. There are many risk factors for ON and more than 1/3 is caused by steroid medications. Presently, there is no proper method to predict the cause of this disease. After the completion of Human Genome Project (HGP), many scientists engage in studying the variations of human gene sequences and one of them is single nucleotide polymorphism (SNP). The variation results in the differences between individuals and may be related with the susceptibility of diseases or drug responses. So far, there are two methodologies to investigate the pathogenesis of ON：Cause that lead to the decrease of blood supply and the defect of bone marrow stroma cell differentiation. Our aim is to analyze the related gene polymorphisms of these two factors and try to identify the risk genotypes of ON than, predict its susceptibility as early as possible. From the hematopoiesis aspect, we choose VEGF, MTHFR, eNOS and PAI-1. In the bone marrow stroma cell differentiation, we select BMP2 and PPARγ2. There are one hundred and nine SLE patients include 21 osteonecrosis patients and 88 non-osteonecrosis patients that were collected from our institution. After analyzing, we found that when combine three susceptibility genotypes include BMP2 (rs3178250) CT type, MTHFR (rs1801133) CC type and VEGF (rs833069) AA type (OR：0.185, 95 % CI：0.044-0.774, p = 0.021) or combine three susceptibility genotypes BMP2 (rs3178250) CT type, MTHFR (rs1801133) CC type and PPARγ2 (rs11128596)AA type (OR：0.096, 95 % CI：0.015-0.597, p = 0.012) or combine three susceptibility genotypes include BMP2 (rs3178250) TT type, VEGF (rs833069) AG type and PPARγ2 (rs11128596) CA type (OR：0.099, 95 % CI：0.016-0.597, p = 0.012) or combine three susceptibility genotypes include VEGF AA type, eNOS 298T GT type and eNOS 27 bp tandem repeat 5R5R type (OR：0.060, 95 % CI：0.006-0.588, p = 0.016), to estimate simultaneously, could predict the possibility of ON formation in SLE patients. The research could provide the molecular epidemiology to study the steroid induced osteonecrosis related genotypes in Taiwanese SLE patients. In the future, we hope to bring out the molecular mechanism of osteonecrosis clearly and correctly. Finally, we hope these genotypes which correlated with osteonecrosis can offer a better tool for doctors to choose the proper medications for treatment.