The Relationship Between Estrogen Receptor Gene Polymorphism With Periodontal Disease And Bone Mineral Density

Periodontal disease, involving microbial encroachment and host responses, are one group of the most common disorders. Chronic periodontitis (CP), is the most one of periodontal disease. It is the inflammatory response to bacteria leads to the destruction of supporting tissue of teeth, characterized by loss of connective tissue and alveolar bone, after that, tooth mobility and abscess may occur, eventually leading to tooth loss. Although bacteria are an initial factor for periodontitis, their impact may be modified by an individual's predisposition. It has been suggested that there is genetic basis and a predisposition for individuals to suffer from CP.Nowadays, most of the association studies have utilized the candidate gene polymorphisms approach to identify the gene variation related to periodontitis. In the last decade a multitude of research projects have been performed to investigate the association between periodontitis and polymorphisms of some genes,including pro- and anti-inflammatory cytokines, innate immune recognition receptor, and some bone metabolism related factors (such as the Vitamin D receptor, MMPs, ER, FcγR, IL-1).Estrogen regulates bone metabolism and triggers a broad array of tissue- and organ- specific physiological responses by binding to a nuclear receptor protein, the ER-αand ER-β. ER is considered the important candidate gene for bone-related diseases. The basic group mutation of ER would cause polymorphisms, formed different genotypes; different genotypes may cause difference of the transcription, or the level of expression or the function of ER receptor. To date, there is a few studies on ER polymorphisms and periodontitis. Therefore, we designed part one of the study.Part one: The association between estrogen receptor and chronic periodontitisA total of 208 unrelated Chinese individuals were selected for the study population, consisting of 109 chronic periodontitis patients and 99 periodontally healthy volunteers serving as the control group. Genomic DNA was extracted from oral mucosa swab sample of each subject by the Chelex-100 method. Determination of the ER polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) with XbaI and PvuII (for ER-α), RsaI and AluI (for ER-β), respectively. The distribution of genotypes and the frequency of alleles were analyzed.Results: The extraction of DNA from swab sample using Chelex-100 is more efficient and rapid than conventional phenol-chloroform extraction for studing genetic polymorphism. And DNA was satisfied to do the further PCR-RFLP experiment. The analysis of the XbaI polymorphisms in ER-αgene revealed significant differences between patients and controls. The detection frequency of XX genotype was significantly higher in the chronic periodontitis patients than in control subjects (22.02% vs. 6.06%, p=0.01). The difference between the female chronic periodontitis patients and healthy controls (29.82% vs. 3.92%, p =0.01) was statistically significant, but no difference was found between the male patients and controls (p = 0.08). Nevertheless, no significant association was noted in the frequency of both RsaI and AluI polymorphisms in ER-βgene and chronic periodontitis. Logistic regression analysis shows that the susceptivity of chronic periodontitis is correlated to age and XbaI gene polymorphisms (p<0.05), but not association with sex, smoking and PvuII, RsaI, AluI gene polymorfisms (p>0.05).Conclusions: It is indicated that the ER-αXX genotype may be a susceptible indicator for chronic periodontitis in female Han Chinese subjects.Osteoporosis is a systemic disorder of decreased skeletal mass and disturbed skeletal architecture and function that result in an increased risk of bone fractures with resultant increased morbidity and mortality. The pathogenesis of osteoporosis is complex and is believed to be an interaction between genetic susceptibility and multiple environmental risk factors, although a number of factors, including hormonal, environmental, and nutritional factors, have been shown to affect BMD. Twin and family studies have revealed that at last 40%-70% of the variation of BMD is accounted for by genetic factors. Periodontitis and Osteoporosis are common disease in post-menopausal women. There are co-risk factors in the two disorders, and the host factor is the current focus. As we known Estrogens play a significant role in bone physiology. Insufficient estrogen is believed to be one of the major causes of postmenopausal osteoporosis (PMO). Osteoporosis is considered as one of the risk factors for periodontal disease and tooth loss. A number of studies have suggested that estrogen may have an important role in chronic inflammatory periodontal diseases. Scholars generally considered that PMO caused by insufficient estrogen is one of the risk factors for periodontitis. Part two: The relationship between the estrogen receptor-αgene polymorphisms and bone mineral density in periodontitis.A total of 145 unrelated Chinese female individuals were selected for the study population, consisting of 65 post-, 80 pre-menopausal female chronic periodontitis patients, and 60 post-menopausal healthy volunteers serving as the control group. Genomic DNA was extracted from oral mucosa swab sample of each subject by the Chelex-100 method. Determination of the ER-αpolymorphisms was performed by PCR-RFLP technique with XbaI and PvuII enzyme. The distribution of genotypes was analyzed. Do dental measures included Clinical attachment loss (CAL), probing pocket depth (PPD).BMD was measured at the spine, femur neck, Ward's triangle and trochanter by dual-energy x-ray absorptiometry (DEXA).statistical analysis the relationship between genotypes and BMD.Results: There was no significant differences between ER-αPvuII, ER-αXbaI genotypes and spine, femur neck, Ward's triangle and trochanter BMD in Post-menopausal CP patients; Meanwhile, there was no significant differences between ER-αPvuII, ER-αXbaI genotypes and spine, femur neck, Ward's triangle and trochanter BMD in Pre-menopausal CP patients(p>0.05); However, there was association between pre- and post- menopausal CP patients (p= 0.027) at Spine L2-L4 BMD; Moreover, there was association between pre- and post- menopausal CP patients (p= 0.004) at Ward's BMD.