Linkage disequilibrium of interleukin-1 genetic polymorphisms with early-onset periodontitis
Linkage disequilibrium of interleukin-1 genetic polymorphisms with early-onset periodontitis
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DOI：
10.1902/jop.1999.70.4.418
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发表时间：
1999-04-01
影响因子：
4.3
通讯作者：
Schenkein, HA
中科院分区：
文献类型：
--
作者：
Diehl, SR;Wang, YF;Schenkein, HA
背景：白细胞介素（IL）-1 α和IL-1 n的基因多态性最近被认为与成人牙周炎的严重程度有关。我们评估这些多态性是否也可能与早发性牙周炎（EOP）在28个非洲裔美国人家庭和7个白人美国家庭与2个或更多的受影响members.Methods：基因组DNA从外周血扩增，然后限制性内切酶消化和丙烯酰胺凝胶电泳，以区分不同片段大小的等位基因。使用了适合于家庭数据的遗传流行病学方法，该方法对由于病例和对照不匹配或不同种族或地理来源的混合亚群而导致的假阳性结果具有鲁棒性。对2种主要的EOP亚型，即局限性青少年牙周炎（WP）和全身性早发性牙周炎（G-EOP，包括快速进展性牙周炎和全身性青少年牙周炎）进行了单独和合并分析。结果：我们获得了非裔美国人和高加索人G-EOP受试者连锁不平衡的高度显着证据。WP也有类似的趋势。与EOP高风险相关的IL-1等位基因以前被认为与严重成人牙周炎的低风险相关。与G-EOP的不平衡对于吸烟和不吸烟的受试者同样强。IL-1a和IL-1 R多态性在高加索人中彼此强烈不平衡，但在非裔美国人中不平衡。同时评估两种多态性的单倍型分析表明，IL-1 n变异可能是EOP风险最重要的。同胞连锁分析，相比之下，只提供了边缘支持EOP风险归因于这些IL-1 polymorphis.Conclusions基因的非常重大的影响：最近的理论分析表明，我们的研究结果是最一致的解释EOP作为一个复杂的，寡基因遗传性疾病，IL-1遗传变异贡献了重要的，但不是唯一的影响疾病的风险。
Background: Genetic polymorphisms at interleukin (IL)-1 alpha and IL-ln were recently suggested to be associated with severity of adult periodontitis. We evaluated whether these polymorphisms might also be associated with early-onset periodontitis (EOP) in 28 African American families and 7 Caucasian American families with 2 or more affected members.Methods: Genomic DNA from peripheral blood was amplified, followed by restriction endonuclease digestion and acrylamide gel electrophoresis to distinguish alleles of different fragment sizes. Genetic epidemiological methods suitable for family data were used that are robust to false-positive findings due to mismatching of cases and controls or mixed subpopulations of different ethnic or geographic origin. The 2 major EOP subtypes, localized juvenile periodontitis (WP), and generalized early-onset periodontitis (G-EOP, encompassing rapidly progressive periodontitis and generalized juvenile periodontitis), were analyzed both separately and together.Results: We obtained highly significant evidence of linkage disequilibrium for both African American and Caucasian G-EOP subjects. A similar trend was noted for WP. The IL-l alleles associated with high risk of EOP had been suggested previously to be correlated with low risk for severe adult periodontitis. Disequilibrium with G-EOP was equally strong for smoking and non-smoking subjects. IL-la and IL-IR polymorphisms were in strong disequilibrium with each other in Caucasians, but not in African Americans. Haplotype analyses evaluating both polymorphisms simultaneously indicated that the IL-ln variant is likely to be most important for EOP risk. Sibpair linkage analyses, by contrast, provided only marginal support for a gene of very major effect on EOP risk attributable to these IL-l polymorphisms.Conclusions: Recent theoretical analyses indicate that our findings are most consistent with an interpretation of EOP as a complex, oligogenic disorder, with IL-l genetic variation contributing an important but not exclusive influence on disease risk.