RESUMO
Chronic periodontitis (CP) is a common oral disease characterized by the slow progression of alveolar attachment loss and bone destruction. Genetic components have been reported to play an important role in the onset and development of CP. In the present study, we aimed to replicate the association signals of NIN and SIGLEC5 identified in previous genome-wide association studies (GWASs) of samples from Chinese Han individuals. Association signals between clinical severity indicators of CP and relevant single nucleotide polymorphisms (SNPs) were also examined. A total of 3,160 study subjects, including 1,076 CP patients and 2,084 healthy controls, were recruited. A total of 32 SNPs, including 22 from NIN and 10 from SIGLEC5, were selected for genotyping. SNPs rs12883458 (OR = 1.45, P = 1.22 × 10-5, NIN) and rs4284742 (OR = 0.75, P = 1.69 × 10-5, SIGLEC5) were significantly associated with CP disease status. rs4284742 was significantly associated with all 3 clinical severity indicators, including bleeding on probing (BOP), probing depth (PD) and clinical attachment loss (CAL). According to evidence from bioinformatics analyses, both significant SNPs, rs12883458 and rs4284742, are likely surrogates of underlying variants with true effects. In summary, our findings provide direct evidence for the association of NIN and SIGLEC5 with CP susceptibility.
Assuntos
Antígenos CD/genética , Antígenos de Diferenciação Mielomonocítica/genética , Periodontite Crônica/genética , Proteínas do Citoesqueleto/genética , Lectinas/genética , Proteínas Nucleares/genética , Adulto , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , China/epidemiologia , Proteínas do Citoesqueleto/metabolismo , Suscetibilidade a Doenças , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/metabolismo , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Interleukin (IL)-8, an important chemokine that regulates the inflammatory response, plays an important role in periodontitis. Previous studies indicate that certain IL-8 gene polymorphisms are associated with periodontitis susceptibility in some populations. However, the literature is somewhat contradictory, and not all IL-8 polymorphisms have been examined, particularly in Han Chinese individuals. The aim of this study was to investigate the association of every IL-8 SNP with chronic periodontitis in Han Chinese individuals. We analyzed 23 SNPs with minor allele frequency (MAF)≥0.01, which were selected from 219 SNPs in the NCBI dbSNP and preliminary HapMap data analyses from a cohort of 400 cases and 750 controls from genetically independent Han Chinese individuals. Single SNP, haplotype and gender-specific associations were performed. We found that rs4073 and rs2227307 were significantly associated with chronic periodontitis. Further haplotype analysis indicated that a haplotype block (rs4073-rs2227307-rs2227306) that spans the promoter and exon1 of IL-8 was highly associated with chronic periodontitis. Additionally, the ATC haplotype in this block was increased 1.5-fold in these cases. However, when analyzing the samples by gender, no significant gender-specific associations in IL-8 were observed, similar to the results of haplotype association analyses in female and male subgroups. Our results provide further evidence that IL-8 is associated with chronic periodontitis in Han Chinese individuals. Furthermore, our results confirm previous reports suggesting the intriguing possibilities that IL-8 plays a role in the pathogenesis of chronic periodontitis and that this gene may be involved in the etiology of this condition.