S100A8 genetic polymorphisms in nuclear families with aggressive periosontitis

Objectives: It has been known that S100A8, a member of S100 calcium-binding protein family, was associated with inflammatory diseases including periodontitis. Our previous population-based study showed an existence of association between polymorphisms rs3795391 (A>G) and rs3806232 (A>G) in the upstream region of the S100A8 gene and aggressive periodontitis (AgP) in Chinese people. This investigation was to analyze and corroborate whether the association also exists in family people.

Methods: Two hundred and four subjects from 73 nuclear families (including 73 probands, 42 fathers, 49 mothers, 35 siblings, 3 grandparents and 2 offspring) were recruited. All probands and their siblings were diagnosed according to 1999 classification of periodontal diseases. Anti-coagulated peripheral blood samples were collected and DNA was extracted. The two SNPs (rs3795391 and rs3806232) of the S100A8 were detected by PCR-RFLP. Analysis of genotype/allele of the two SNPs was performed by Family-Based Association Test (FBAT) software. The program uses standard genetic models (additive, dominant or recessive) to test association.

Results: The Hardy-Weinberg Equilibrium was satisfied for two SNPs. (rs3795391: x2=0.43, P=0.51; rs3806232: x2=1.18, P=0.277). There was a statistically significant association of the SNP rs3795391 with AgP under additive genetic model (chi2= 3.9836, df =1, P = 0.0459). Eighteen informative families (i.e., families at least one heterozygous parent) were included under the additive model. Allele A of the SNP rs3795391 showed significantly preferential transmission to the affected individuals of AgP (Z = 1.996, P = 0.0459). The other SNP rs3806232 showed no significant results under all three models tested.

Conclusions: This family-based association study supports the association that genetic polymorphisms of S100A8 gene may have an impact in AgP susceptibility.

This research was supported by the National High Tech Program (‘‘863'' Program) (2002AA217091); Clinical Research Fund, Ministry of Health P.R.C. National Scientific and Technical Supporting Program in the 11th Five-Year Period (2007BAI18B02)