Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, PR China.
Clin Exp Hypertens. 2012;34(5):377-82. doi: 10.3109/10641963.2012.665538. Epub 2012 Apr 3.
Ficolin-3, encoded by FCN3, is the predominant recognition molecule of lectin pathway for the activation of complement component 3 (C3), which is an important risk factor for the development of hypertension. In our previous study, we found the complement system including ficolin-3 was overrepresented in the serum of type 2 diabetic patients. Since type 2 diabetes shares some pathogenic components, including excessive serum C3, with hypertension, this study aims to test the hypothesis that common variants at FCN3 might be associated with essential hypertension in our Chinese population. A total of 1797 subjects were recruited. Of them, 573 were with essential hypertension. Based on HapMap data, three tagging single nucleotide polymorphisms (rs2504778, rs10794501, and rs3813800) in FCN3/CD164L2 region were selected for genotyping by using MassARRAY. Logistic regression analysis was performed to evaluate the genetic effects on the prevalence of hypertension after adjusting for covariates. rs2504778, which locates in the upstream of FCN3 and in the intron of CD164L2, was found to be significantly associated with hypertension after adjusting for covariates (OR = 1.28, 95% CI: 1.05, 1.55, P = .015). Correction for multiple testing did not remarkably attenuate the significance (empirical P = .042 with 10 000 permutations). rs2504778 also showed a nominal association with systolic blood pressure (P = .044) in the quantitative trait analysis. No evidence of correlation with hypertension and blood pressure was observed for rs10794501 and rs3813800. We found that a common variant of FCN3/CD164L2 is associated with hypertension in our Chinese population. More studies with larger sample size are needed to confirm this finding.
ficolin-3 由 FCN3 编码，是补体成分 3（C3）激活途径的主要识别分子，而 C3 是高血压发展的重要危险因素。在我们之前的研究中，我们发现补体系统包括 ficolin-3 在 2 型糖尿病患者的血清中过度表达。由于 2 型糖尿病与高血压共享一些致病成分，包括过量的血清 C3，因此本研究旨在检验 FCN3 常见变异可能与中国人群原发性高血压相关的假设。共招募了 1797 名受试者，其中 573 名患有原发性高血压。基于 HapMap 数据，选择 FCN3/CD164L2 区域的三个标记单核苷酸多态性（rs2504778、rs10794501 和 rs3813800），使用 MassARRAY 进行基因分型。通过逻辑回归分析，在调整协变量后，评估遗传因素对高血压患病率的影响。rs2504778 位于 FCN3 的上游和 CD164L2 的内含子中，在调整协变量后，与高血压显著相关（OR=1.28，95%CI：1.05，1.55，P=0.015）。进行 10000 次随机置换检验校正多重检验后，其显著性并未明显减弱（经验 P=0.042）。在定量性状分析中，rs2504778 与收缩压也存在显著相关性（P=0.044）。rs10794501 和 rs3813800 与高血压和血压均无相关性。我们发现，FCN3/CD164L2 的一个常见变异与中国人群的高血压相关。需要更大样本量的研究来证实这一发现。
