Family-based association analysis of S100A8 genetic polymorphisms with aggressive periodontitis

It is known that S100A8, a member of the S100 calcium-binding protein family, is associated with inflammatory diseases, including periodontitis. Our previous population-based study found an association between two polymorphisms, rs3795391 (A > G) and rs3806232 (A > G), in the upstream region of the S100A8 gene and aggressive periodontitis (AgP) in Chinese people. Based on those results, this investigation set out to analyze and corroborate whether the association also exists within families.

Two hundred and four subjects from 73 nuclear families were recruited. All probands and their relatives were diagnosed according to the 1999 classification of periodontal diseases. Anticoagulated peripheral blood samples were collected from all the subjects, and DNA was extracted. The two single nucleotide polymorphisms (SNPs; rs3795391 and rs3806232) were detected and analyzed by standard polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Analysis of genotype/allele was performed by Family-Based Association Test (FBAT) software ( http://www.biostat.harvard.edu/~fbat/default.html).

There was a statistically significant association of the SNP rs3795391 with AgP in the additive genetic model (chi(2) = 3.9836, d.f. = 1, p = 0.0459). Allele A showed significantly preferential transmission to the AgP affected individuals (Z = 1.996, p = 0.0459). The other SNP, rs3806232, showed no significant results in all models.

This family-based association study supports the previous findings that SNP rs3795391 (A > G) of the S100A8 gene might contribute to AgP susceptibility. This is, to our knowledge, the first investigation about AgP using FBAT in genetic analysis.