台灣女性SPP1基因多型性與骨密度低下之關聯研究

Abstract

背景：Secreted phosphoprotein-1 (SPP1) 骨橋蛋白基因，藉由和破骨細胞膜表面的vitronectin受體結合，參與破骨細胞接合骨質的破骨作用中。最近的統合分析發現，SPP1基因多型性與骨密度及骨折的風險有關。 方法：這是一篇橫斷式研究。 1319位健康台灣女性，年齡在40至55歲，於2009年10月至2010年8月間，從美兆健康體檢中心被招募。高與低骨密度比較，高骨密度定義為三等分的第一組，而第二組加上第三組則為低骨密度。本研究探討三種常見的(對偶基因頻率> 5%) haplotype-tagging單核苷酸多型性(htSNP)來分析SPP1基因多型性與低骨密度風險的關聯。我們還評估了更年期，年齡，身體質量指數和相關的生物標誌物如何影響SPP1多型性與低骨密度風險之間的相關 結果：研究結果顯示帶有rs4754變異的對偶基因會降低低骨密度風險[2 vs. 0 copies: adjust odds ratio（AOR）= 0.54，95％CI= 0.36 - 0.81]，與非攜帶者相比，攜帶兩個變異的婦女有較高的骨密度。在單倍體分析方面，在校正偽陽性率後，攜帶HAP1 TGC兩個變異的婦女在高鹼性磷酸酶 [AOR= 0.30，95％CI= 0.15 - 0.64]和或低尿酸 [AOR= 0.33，95％CI= 0.16 - 0.68] 時有保護的效果。 SPP1基因和低骨密度風險，無論是在單核苷酸多型性或單倍體水平沒有顯著作用。在本研究中，停經與否並不會顯著的修飾SPP1基因與低骨密度的關係。 結論：在中年亞裔女性身上，SPP1基因多型性與保護骨密度低下有顯著的相關。

Background. Secreted phosphoprotein-1 (SPP1) is involved in the anchoring of osteoclasts to the mineral of bone matrix by binding with vitronectin receptor. A recent meta-analysis found SPP1 genetic polymorphisms were associated with bone mineral density (BMD) and fracture risk. Methods. This is a cross-sectional study. A total of 1,319 healthy Taiwanese women aged 40 to 55 years old were recruited from MJ health screening center from October 2009 to August 2010. High versus low bone mineral density (BMD) was defined as the 1st tertile versus 2nd plus 3rd tertiles of BMD. Three common (allele frequency>5%) haplotype-tagging single nucleotide polymorphisms (htSNPs) were selected to examine the association between sequence variants of SPP1 and BMD. Results. Women carrying two copies of variant rs4754 had a significantly decreased risk of low BMD [adjusted OR (AOR) = 0.54, 95% CI = 0.36 - 0.81] as compared with non-carriers. Women carrying two copies of minor haplotype TGC had a decreased risk of low BMD among those with high alkaline phosphatase [AOR = 0.30, 95% CI = 0.15 - 0.64] or with low uric acid [AOR = 0.33, 95% CI = 0.16 - 0.68]. These associations remained significantly associated with low BMD after controlling for FDR. Menopausal status did not significant modify the association between SPP1 polymorphisms and low BMD. Conclusion . Genetic polymorphisms of SPP1 were significantly associated with decreased risk of low BMD in middle-aged Asian women.