한국인의 혈관내피성장인자 3` 비번역 부위의 유전자 다형성과 당뇨망막증과의 상관성

목적 : 혈관 내피성장인자(VEGF) 및 그 수용체(VEGFR)의 단일염기변이(Single nucleotide polymorphism, SNP)와 당뇨망막병증과의 상관성을 확인하고자 하였다. 대상과 방법 : 당뇨병환자 총 96명(증식당뇨망막병증(PDR), n=32; 비증식당뇨망막병증(NPDR), n=25; 비당뇨망막병증(no DMR), n=39)을 대상으로 VEGF 및 VEGFR의 SNP를 matrix assisted laser desorption time of flight mass spectrometry (MALDI-TOF)를 이용하여 분석하였다. 결과 : VEGF의 3’-untranslated regions (3’-UTR) 부위 내 SNP인 vf1과 vf2는 complete linkage를 보였으며, 당뇨망막병증 환자(38.6%)에서 비당뇨망막병증 환자(17.95%)에 비해 rare allele (T)이 높은 빈도로 나타났다(p=0.030). VEGFR의 3’-UTR 부위 내 SNP인 vfr1도 당뇨망막병증 환자(19.3%)에서 비당뇨망막병증 환자(5.13%)에 비해 rare allele (A)가 높은 빈도로 나타났다(p=0.046). 하지만, 세 가지 SNP는 당뇨망막병증 환자 내에서 NPDR 과 PDR군간에는 빈도의 차이를 보이지 않았다. 결론 : 이러한 결과는 VEGF와 VEGFR의 3’-UTR 부위 내 SNP가 당뇨망막병증 발현과 관련되어있음을 시사한다. Purpose: Recent studies suggest that increased expression of the vascular endothelial growth factor (VEGF) may play a role in the pathogenesis of diabetic complications. The aim of this study was to assess the potential association of VEGF gene polymorphisms with disease expression of retinopathy in patients with diabetes mellitus. Methods: We studied 96 diabetic patients to determine whether there is an association between diabetic retinopathy in VEGF and VEGFR gene; all patients were unrelated Korean individuals (PDR, n=32; NPDR, n=25; no DMR, n=39). We analyzed VEGF and VEGFR SNP by restriction fragment mass polymorphism (RFMP). PCR was performed with primers designed to introduce a type IIS restriction endonuclease recognition sequence (FokI, BstF5I) ahead of the polymorphism site. The enzymatic cleavage of the products resulted to excision of two oligonucleotide fragments containing the variation site, and then masses of the resulting oligonucleotide fragments were examined by matrix assisted laser desorption time of flight mass spectrometry (MALDI-TOF MS). Difference are seen as the presence, absence, or mass change in peaks corresponding to the fragments affected by existence of polymorphism that have base substitution at the site of variation. Results: We found that the genotype frequencies of two polymorphisms shown to be completely linked to each other (rs3025039; vf1, rs3025040; vf2) and one polymorphism (rs3812867; vfr1) within 3'-untranslated regions (3'-UTR) of the VEGF and VEGFR1 significantly differed between patients with and without retinopathy. The frequencies of the vf1, vf2 and vfr1 did not differ significantly between the NPDR and PDR group Conclusions: These data implicate the polymorphisms in the 3'-UTR of the VEGF and VEGFR1 g