Teeuw Wijnand J, Laine Marja L, Bizzarro Sergio, Loos Bruno G
Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Amsterdam, the Netherlands.
PLoS One. 2015 Sep 8;10(9):e0137335. doi: 10.1371/journal.pone.0137335. eCollection 2015.
Elevated high sensitive C-reactive protein (hsCRP) is a marker for systemic inflammation and a risk marker for atherosclerotic cardiovascular disease (ACVD), and has also been associated with periodontitis. Inter-individual variation for hsCRP in periodontitis has been shown. ANRIL is the strongest genetic susceptibility locus for both periodontitis and ACVD, and it is speculated that genetic variation in ANRIL may modulate inflammatory processes. Therefore, we explored the possible association between hsCRP plasma levels and a leading ANRIL single nucleotide polymorphism (SNP) in periodontitis patients and controls. 171 healthy subjects with North European descent (115 periodontitis and 56 controls) were included in this case-control study. hsCRP levels were determined and subjects were genotyped for the leading ANRIL SNP rs1333048. In a multivariate analysis, periodontitis, female gender, increasing BMI and homozygosity for the major allele (AA-genotype) of rs1333048 were significantly associated with elevated hsCRP plasma levels (p = 0.012, p = 0.004, p = 0.007 and p = 0.003, respectively). Periodontitis patients with rs1333048 AA-genotype showed higher levels of hsCRP than those carrying the minor C allele (median: 4.5 mg/L vs. 1.6 mg/L, padjusted = 0.007). This study is the first to show that, in addition to gender and BMI, also a leading SNP in ANRIL is explanatory for inter-individual variation in hsCRP levels in periodontitis patients of North European descent.
高敏C反应蛋白（hsCRP）升高是全身炎症的标志物和动脉粥样硬化性心血管疾病（ACVD）的风险标志物，并且也与牙周炎有关。牙周炎患者中hsCRP的个体间差异已得到证实。ANRIL是牙周炎和ACVD最强的遗传易感性位点，据推测ANRIL的基因变异可能调节炎症过程。因此，我们探讨了牙周炎患者和对照组中hsCRP血浆水平与ANRIL主要单核苷酸多态性（SNP）之间的可能关联。这项病例对照研究纳入了171名具有北欧血统的健康受试者（115名牙周炎患者和56名对照）。测定了hsCRP水平，并对受试者进行了ANRIL主要SNP rs1333048的基因分型。在多变量分析中，牙周炎、女性性别、体重指数增加以及rs1333048主要等位基因（AA基因型）的纯合性与hsCRP血浆水平升高显著相关（分别为p = 0.012、p = 0.004、p = 0.007和p = 0.003）。rs1333048 AA基因型的牙周炎患者的hsCRP水平高于携带次要C等位基因的患者（中位数：4.5 mg/L对1.6 mg/L，校正p = 0.007）。这项研究首次表明，除了性别和体重指数外，ANRIL中的一个主要SNP也可解释北欧血统牙周炎患者hsCRP水平的个体间差异。
