In conclusion,thisstudy providesevidenceforan association between VEGF polymorphisms and the risk ofosteoporotic vertebralcompression fractures in postmenopausalwomen in the current study population.In particular,VEGF -2578AA was a protective marker in our study,because -2578CC induced a higherconcentration ofhomocysteinein thepatientgroup.In thepatientgroup, the TSER,2R3R+2R2R/TS,3'-UTR and 0bp6bp+6bp6bp combination genotype was found to be of marginal significance. Its significance may fluctuate according tosamplesize.Therefore,largeprospectiveandheterogeneousstudies willbenecessary tosupportthefindingsofthisstudy.Theauthoriscurrently testing this hypothesis and assessing the associations among VEGF gene polymorphisms,fractureriskanddietaryintakeormetabolicsyndrome.
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국문요약
-폐경 후 골다공성 척추압박골절 환자의 유전자 다형 관련성
아주대학교 대학원 의학과
정 영 선
(지도교수:조 기 홍)
혈관내피세포 성장인자 (Vascularendothelialgrowth factor;VEGF) 는 혈관신생 (angiogenesis)을 통한 골 형성에 관여하며 골절의 치유를 촉진한다.고 호모시스테인혈증 (hyperhomocysteinemia)은 골다공증,뼈 의 무기질 밀도의 저하 및 골절 등과 같은 골격계에 문제를 일으키는 위 험인자로 알려져 있다. 5, 10-methylenetetrahydrofolate reductase (MTHFR)와 thymidylatesynthase (TS)효소는 모두 호모시스테인 대 사과정에 관여한다.따라서 본 연구자는 VEGF,MTHFR 및 TS의 유전 자 다형 (polymorphism)이 한국여성의 폐경 후 골다공성 척추 압박골절 (osteoporotic vertebralcompression fracture;OVCF)과 관련이 있는지 알아보고자 하였다.한국여성의 폐경 후 골다공성 척추 압박골절 환자 82명과 골절이 없는 폐경 후 여성 117명을 대조군으로 하여 실시하였다.
VEGF, MTHFR 및 TS 유전자 다형을 polymerase chain reaction -restriction fragmentlength polymorphism (PCR-RFLP)와 real-time PCR을 통하여 분석하였다.VEGF 유전자의 다형이 호모시스테인/엽산
(homocysteine/folate)대사에 영향을 주는지 여부를 혈중 호모시스테인 농도를 측정하여 확인하였다.VEGF -2578C>A 다형 중 -2578AA 유전 자형 (genotype)이 대조군에 비해 통계적으로 의미 있는 차이를 보였다.
VEGF -1154G>A,-634G>C와 936C>T 유전자 다형에서는 별다른 차이 를 보이지 않았다.그런데 A-G-G-C 일배체유전자형 (haplotype)은 한 국여성의 폐경 후 골다공성 척추 압박골절의 발병에 관련된 경향을 발견 하였다.그리고 VEGF -2578C>A 유전자 다형은 혈중 호모시스테인 농 도와도 연관되어 있었다.그러나 MTHFR과 TS 유전자 다형은 골다공 성 척추 압박골절과의 관련성은 발견할 수 없었다.결론적으로,VEGF -2578C>A 유전자 다형과 일부 일배체 유전자 (A-G-G-C)은 한국여성 의 폐경 후 골다공성 척추 압박골절 발병 위험인자로 중요한 역할을 한 다고 할 수 있겠다.
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핵심어:혈관내피성장인자,골다공성 척추 압박골절,폐경여성,유전자 다형,호모시스테인