Dwi Anita Suryandari

Gene promoter polymorphism of RUNX2 and risk of osteoporosis in postmenopausal Indonesian women

Objectives: Osteoporosis is a metabolic bone disease of reduced bone mass density (BMD) and elevated risk of fracture due to an imbalance in bone formation and resorption. The risk and incidence of osteoporosis increase towards advanced age, particularly in postmenopausal women, and the risk is known to be affected by the variation in the expression of the associated regulatory genes. This work aimed to clarify the impact of variation in RUNX2 (runt domain transcription factor 2), which is an osteoblast-specific transcription factor that normally stimulates bone formation and osteoblast differentiation, regarding single-nucleotide polymorphism within RUNX2 promoter (P1) and risk of osteoporosis in postmenopausal Indonesian women. Methods: Using DNA sampling from blood, the variation at the single-nucleotide polymorphism (-330, G→T, rs59983488) at the RUNX2 P1 promoter was investigated using polymerase chain reaction–restriction fragment length polymorphism for 180 consenting postmenopausal Indonesian women. The subjects were examined for bone mass density and classification to normal and those with osteopenia or osteoporosis by T-scoring with dual-energy X-ray absorptiometry. Chi-square testing and logistic regression were mainly used for statistical assessment. Results: The results showed a general trend with increased risk of osteoporosis associated with the genotype TT (mutant type) and the corresponding T allele of the tested polymorphism of RUNX2 promoter P1. The trend was, however, not significant in multivariate testing adjusted for age and time after menopause. Conclusion: To confirm the potential risk with TT genotype would require testing of a much larger sample of subjects. As the tested single-nucleotide polymorphism only represents one of the relevant candidate locations of RUNX2, the results are taken nevertheless to suggest an impact by overall RUNX2 variation in the risk of osteoporosis in Indonesian postmenopausal women.

CRP and IL-1B Gene Polymorphisms and CRP in Blood in Periodontal Disease

Recent studies have suggested an association between periodontal disease (PD) and the systemic polygenic diseases such as cardiovascular disease (CVD). These are thought to be associated because of interrelated environmental, epigenetic, and genetic risk factors. The involved candidate genes include the IL-1B gene, encoding the pro-inflammatory cytokine IL-1β, and the CRP gene encoding the C-reactive protein (CRP), also a known marker of inflammation. However, as the details are not well known on the genetic variation influencing the risk factors, this work aimed to evaluate the distribution of selected polymorphisms of IL-1B and CRP genes, and serum CRP level, in comparison with the PD status. For this purpose, periodontal health was assessed, serum CRP levels measured and polymorphism status of IL-1B and CRP genes determined from samples of peripheral blood taken from 101 consenting Indonesian adult males. The results show that severe PD was significantly associated with age and smoking, as expected, but not with the polymorphisms of IL-1B or CRP (1444). However, a significantly lower fraction of subjects with normal periodontal health than subjects with PD showed the heterozygous type polymorphism of CRP (717). There was no significant difference in the fraction of cases with elevated serum CRP level between subjects with normal health and those with PD, and further study with a larger sample is recommended. The observed association between polymorphism of CRP (717) and periodontal health is suggested as a complementary indicator of the risk to PD for the Indonesian male population.