유지 혈액투석 환자에서 KLOTHO 유전자다형성과혈중 osteoprotegerin치와의 관계 = The Association of KLOTHO Gene Polymorphism with SerumOsteoprotegerin Levels in Maintenance Hemodialysis Patients

다국어 초록 (Multilingual Abstract)

Purpose : Klotho mutant mice showed abnormal calcium and vitamin D metabolism, hyperphosphatemia and vascular calcification. We observed the frequencies of klotho gene polymorphism and investigated their relation with some clinical parameters including serum osteoprotegerin (OPG) levels in maintenance hemodialysis (HD) patients.
Methods : Total 88 patients (mean age 58±13 years, male:female=47:41) on maintenance HD were enrolled. The genotypings for G-395A in promoter and C1818T in exon 4 of klotho gene were performed with real-time polymerase chain reaction. We measured blood pressure, body mass index (BMI), and serum calcium, phosphorus, parathyroid hormone (PTH), alkaline phosphatase, hs-CRP, lipid profiles and OPG.
Results : In G-395A in promoter, the distribution of genotypes was GG 66% (n=58), GA 23% (n=20) and AA 11% (n=10), respectively and the allele frequencies were 0.773 for G allele and 0.227 for A allele. In C1818T in exon 4, the distribution of genotypes was CC 63% (n=55), CT 30% (n=26), and TT 7% (n=7), and the frequencies were 0.773 for C allele and 0.227 for T allele. G-395A shows correlations with BMI and HDL-cholesterol (p<0.005). G-395A and C1818T in klotho gene show no statistical correlation with other clinical parameters of vascular calcification including OPG.
Conclusion : Klotho G-395A and C1818T polymorphisms are not correlated with OPG in maintenance HD patients. Further research needs for the other klotho polymorphisms on chronic kidney disease and end-stage renal disease.

국문 초록 (Abstract)

목 적 : 최근 Klotho 변이 쥐에서는 칼슘과 비타민D 대사 이상을 보여 고인산혈증과 혈관 석회화를 나타난다고 보고되었다. Klotho 변이 쥐에서 보이는 동맥경화증은 혈관 석회화의 표지자로 알려진 Osteoprotegerin (OPG)가 결핍된 쥐에서와 유사한 표현형을 보인다. 본 연구에서는 혈액투석 중인 환자에서 Klotho promoter 부위의 G-395A와 exon 4의 C1818T 유전자다형성의 빈도를 관찰하고, OPG를 비롯한 임상지표와의 연관성을 알아보았다. 방 법 : 유지 혈액투석 환자 88명 (평균나이 58±13세, 남:여=47:41)을 대상으로 혈압과 체질량지수, 칼슘, 인, 부갑상선 호르몬, 알칼리 포스파타제, hs-CRP 및 지질검사를 시행하였다. 혈중 OPG는 ELISA (enzyme-linked immunosorbent assay)를 이용하여 측정하였고, klotho 유전자형은 실시간 중합효소 연쇄반응 (real-time polymerase chain reaction)을 이용하여 분석하였다.결 과 : G-395A 유전자다형성은 각각 GG 66% (n=58), GA 23% (n=20), AA 11% (n=10)이었고, G allele의 빈도는 0.773, A allele 빈도는 0.227이었다. C1818T 유전자다형성에서는 CC 63% (n=55), CT 29% (n=26), TT 8% (n=7)이었고, C allele 빈도는 0.773, T allele 빈도는 0.227이었다. G-395A는 체질량지수와 고밀도지단백 콜레스테롤과 유의한 상관관계를 보였으나 (p<0.05), G-395A와 C1818T는 OPG를 비롯한 다른 혈관석회화의 임상변수들과 통계학적으로 유의한 상관관계는 없었다.

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