Complement factor H and hemicentin-1 in age-related macular degeneration and renal phenotypes
Complement factor H and hemicentin-1 in age-related macular degeneration and renal phenotypes
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DOI：
10.1093/hmg/ddm164
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发表时间：
2007-09-01
影响因子：
3.5
通讯作者：
Iyengar, Sudha K.
中科院分区：
文献类型：
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作者：
Thompson, Cheryl L.;Klein, Barbara E. K.;Iyengar, Sudha K.
在这项研究中，我们研究了补体因子 H (CFH) 和 hemicentin-1 (HMCN1) 与年龄相关性黄斑变性 (AMD) 和肾功能的关系。在两个样本中检查了测量 AMD 和玻璃疣发展过程的三个量表：家庭年龄相关性黄斑变性研究 (FARMS)，由通过患有严重 AMD 的单个个体确定的家庭组成；以及未确定的基于人群的家庭队列，海狸坝眼科研究 (BDES)，该研究也用于评估 AMD 的纵向变化以及与肾功能的关联。通过考虑已知风险因素以及家庭和兄弟姐妹影响的回归来进行关联。 rs1061170 (Y402H) 变异与 AMD 相关的有力证据得到证实（BDES 中 P = 9.15 x 10(-5)，FARMS 中 P = 0.016）。在多种 AMD 量表中观察到这种关联，表明其作用不具有表型特异性。 CFH 和 HMCN1 的多态性似乎影响 AMD 的纵向变化率。 rs1061170 多态性还与估计肾小球滤过率 (eGFR) 的降低相关 (P = 0.046)。另一个 CFH 多态性 rs800292 与 eGFR 类似地相关 [β = - 0.90 (P = 0.022)]。还观察到 HMCN1 中 rs743137 (P = 0.05) 和 rs680638 (P = 0.022) 与计算的肌酐清除率进展之间的关联。这两个基因似乎在 AMD 和肾脏病理生理学中都发挥着作用。这些发现支持了影响眼和肾功能的常见途径的证据，并表明需要对其共同决定因素进行进一步的研究。
In this study, we investigated the associations of complement factor H (CFH) and hemicentin-1 (HMCN1) with age-related macular degeneration (AMD) and renal function. Three scales, measuring the course of AMD and drusen development, were examined in two samples: the Family Age-Related Macular degeneration Study (FARMS), consisting of families ascertained through a single individual with severe AMD, and an unascertained population-based family cohort, the Beaver Dam Eye Study (BDES), which was also used to assess longitudinal changes in AMD and associations with renal function. Associations were performed by a regression accounting for known risk factors as well as familial and sibling effects. Strong evidence of the association of rs1061170 (Y402H) variation with AMD was confirmed (P = 9.15 x 10(-5) in BDES, P = 0.016 in FARMS). This association was observed in multiple AMD scales, suggesting that its role is not phenotype-specific. Polymorphisms in both CFH and HMCN1 appeared to influence the longitudinal rate of change of AMD. The rs1061170 polymorphism was also associated with a reduction in estimated glomerular filtration rate (eGFR) (P = 0.046). Another CFH polymorphism, rs800292, was similarly associated with eGFR [beta = - 0.90 (P = 0.022)]. Associations between rs743137 (P = 0.05) and rs680638 (P = 0.022) in HMCN1 with calculated creatinine clearance progression were also observed. Both genes appear to play a role in both AMD and renal path ophysiology. These findings support evidence for common pathways influencing ocular and renal function and suggest that further work is required on their common determinants.