Iber-Díaz Paula, Senen-Carramolino Raquel, Iglesias-Linares Alejandro, Fernández-Navarro Pablo, Flores-Mir Carlos, Yañez-Vico Rosa M
Section of Orthodontics, School of Dentistry, Complutense University, 28040 Madrid, Spain.
BIOCRAN Craniofacial Biology Research Group, Complutense University, 28040 Madrid, Spain.
J Pers Med. 2020 Oct 14;10(4):169. doi: 10.3390/jpm10040169.
Personalized dental medicine requires from precise and customized genomic diagnostic. To conduct an association analysis over multiple putative loci and genes located at chromosomes 2, 4, 8, 12, 18, X, and Y, potentially implicated in an extreme type of external apical root resorption secondary to orthodontic forces (aEARR). A genome-wide association study of aEARR was conducted with 480 patients [ratio~1:3 case/control]. Genomic DNA was extracted and analyzed using the high-throughput Axiom platform with the GeneTitan MC Instrument. Up to 14,377 single nucleotide polymorphisms (SNPs) were selected at candidate regions and clinical/diagnostic data were recorded. A descriptive analysis of the data along with a backward conditional binary logistic regression was used to calculate odds ratios, with 95% confidence intervals [ < 0.05]. To select the best SNP candidates, a logistic regression model was fitted assuming a log-additive genetic model using R software [ < 0.0001]. In this sample the top lead genetic variants associated with aEARR were two novel putative genes located in the X chromosome, specifically, STAG 2 gene, rs151184635 and RP1-30E17.2 gene, rs55839915. These variants were found to be associated with an increased risk of aEARR, particularly restricted to men [OR: 6.09; 95%CI: 2.6-14.23 and OR: 6.86; 95%CI: 2.65-17.81, respectively]. Marginal associations were found at previously studied variants such as : rs11730582 [OR: 0.54; 95%CI: 0.34-0.86; = 0.008], : rs1718119 [OR: 0.6; 95%CI: 0.36-1.01; = 0.047], and : rs8086340 [OR: 0.6; 95%CI: 0.38-0.95; = 0.024]), found solely in females. Multiple putative genetic variants located at chromosomes X and Y are potentially implicated in an extreme phenotype of aEARR. A gender-linked association was noted.
个性化牙科医学需要精确且定制化的基因组诊断。为了对位于2号、4号、8号、12号、18号染色体、X染色体和Y染色体上的多个假定基因座和基因进行关联分析，这些基因座和基因可能与正畸力继发的一种极端类型的根尖外吸收（aEARR）有关。对480名患者[病例/对照比例约为1:3]进行了aEARR的全基因组关联研究。提取基因组DNA并使用配备GeneTitan MC仪器的高通量Axiom平台进行分析。在候选区域选择了多达14377个单核苷酸多态性（SNP），并记录了临床/诊断数据。对数据进行描述性分析，并使用向后条件二元逻辑回归计算优势比，95%置信区间[<0.05]。为了选择最佳的SNP候选基因，使用R软件[<0.0001]拟合了一个假设对数加性遗传模型的逻辑回归模型。在这个样本中，与aEARR相关的主要遗传变异是位于X染色体上的两个新的假定基因，具体来说，是STAG 2基因，rs151184635和RP1-30E17.2基因，rs55839915。发现这些变异与aEARR风险增加相关，尤其仅限于男性[优势比分别为：6.09；95%置信区间：2.6 - 14.23和6.86；95%置信区间：2.65 - 17.81]。在先前研究的变异中发现了边缘关联，如：rs11730582[优势比：0.54；95%置信区间：0.34 - 0.86；P = 0.008]、rs1718119[优势比：0.6；95%置信区间：0.36 - 1.01；P = 0.047]和rs8086340[优势比：0.6；95%置信区间：0.38 - 0.95；P = 0.024]，这些仅在女性中发现。位于X染色体和Y染色体上的多个假定遗传变异可能与aEARR的一种极端表型有关。注意到了与性别相关的关联。
