Investigation On Polymorphisms Of Interleukin-6 And Interleukin-1 Genes As The Risk Factors For Coronary Heart Disease And Chronic Periodontitis

Coronary heart disease(CHD)is a kind of multifactorial chronic diseases.In CHD,infections including of periodontal infection and other body infections are proposed to be risk factors.Inflamation plays a central role in atherogenesis from endothelial cell expression of inflammatory cytokines,platelet adhesion and aggregation,smooth muscles cells and connected tissues proliferation to the development of the atherosclerosis.Chronic periodontitis is an inflammatory disease and is the most frequently occurring form of infections in adults.A growing body of studies support significant associations between periodontal diseases and CHD and it was concluded that periodontal disease was modestly associated with atherosclerosis, myocardial infarction,and cardiovascular events.CHD and chronic periodontitis both are considered as complex chronic diseases related to multiple genes,and associated with inflamation.Thus,it is postulated that periodontitis and CHD may share the common genetic background.Identifying these genes can therefore result in novel diagnostics for risk assessment,early detection, individualized treatment approaches for the two diseases especially for CHD. Interleukin-l(IL-1)and interleukin-6(IL-6)both are potent inflammatory agents.In the past 20 years,plenty of studies from periodontal research or cardiovascular research separately reported that genetic polymorphisms in the genes regulating IL-lor IL-6 had been associated with increased susceptibility to moderate-severe chronic periodontitis and CHD,but very few investigations had mentioned that the presence of genotypes of interleukin-6 or interleukin-1 directly increases the developing and severity of both periodontitis and CHD.However,the subjects enrolled in the most studies were Europen or American-Africans,it is still not clear whether polymorphisms of interleukin-6 gene or interleukin-1 gene are associated with the susceptibility or severity of both moderate-severe chronic periodontitis and CHD in Chinese han population.The purpose of the study was to investigate that interleukin-1 gene polymorphisms at positions IL-1B+3954C/T,IL-1B-511C/T,IL-1A+4845G/T and interleukin-6 gene polymorphisms at positions IL-6-174G/C,IL-6-572C/G,IL-6-597G/A and the association of moderate-severe chronic periodontitis and coronary heart disease.The genotype and allele distributions of interleukin-1 and interleukin-6 in a case-control study involving four groups(moderate-severe chronic periodontitis and CHD group, merely CHD group,merely moderate-severe chronic periodontitis group and health control)were analyzed by polymerase chain reaction-restriction fragment length polymorphism.Relationships between the distributions of the genotypes and risk factors were also investigated.The results showed:(1)The frequencie of T allele at the site IL-1A+4845 was 6.5%,IL-1B+3954 T allele frequencie was 1.7%, IL-1B-511 T allele frequencie was 49.5%,IL-6-174 C allele frequencie was 0.5%, IL-6-597 A allele frequencie was 0%,IL-6-572 G allele frequencie was 20.1%).(2) There were no significant differences in genotype or allele frequencies between 4 groups for IL-1A+4845G/C polymorphisms(genotype:x~2=3.811 p=0.702,allele: X2=3.285 p=0.350),IL-1B+3954C/T polymorphisms(genotype:x2=3.918 p=0.270, allele:x2=3.849 p=0.278),IL-6-174G/C polymorphisms(genotype:x2=0.092 p=0.993,allele:x2=0.092 p=0.993)and IL-6-597G/A polymorphisms(only one genotype was detected).(3)There were also not any significant differences in genotype or allele frequencies among moderate chronic periodontitis and severe chronic periodontitis group and health control for IL-1B-511C/T polymorphisms (genotype:x2=3.426 p=0.489,allele:x2=1.444 p=0.486),but statistically significant differences were found between coronary heart disease groups and no coronary heart disease groups(x2=20.602 p=0.000),CT+CC genotype resulted in an increased risk(ORcr+cc/rr=2.876;95%CI:1.759-4.702)? C allele at the site IL-1B-511 was significantly higher in coronary heart disease groups(x2=6.907 p=0.009 ORC/t=1.411;95%CI:1.091-1.824).IL-1B-511 gene polymorphisms were significantly associated with CHD in the absence of other risk factors such as hypertension,hyperlipidema,alcohol drinking.(4)No significant differences in genotype or allele frequencies for IL-6-572C/G polymorphisms was detected between moderate chronic periodontitis group and severe chronic periodontitis group and health control(genotype:x2=4.771 p=0.312,allele:x2=l-465 p=0.481),but statistically significant differences were found between coronary heart disease groups and no coronary heart disease groups(x2=13.367,p=0.001),GG+CG genotype resulted in an increased risk(ORGg+cg/cc=1.985;95%CI:1.370-2.876).G allele at the site IL-6-572 was significantly higher in coronary heart disease groups(x2=12.326 p=0.000,ORG/c=1.737;95%CI:1.274-2.369).IL-6-572 gene polymorphisms were significantly associated with CHD in the absence of other risk factors such as smoking,hypertension,hyperlipidema and alcohol drinking. This study came to the following conclusions:Mutations at the position+3954 of interleukin-1,+4845 of interleukin-1,-174 of interleukin-6,-597 of interleukin-6 were rare in GuangDong Han population.Interleukin-1-511C/T and interleukin-6 -572C/G polymorphisms did not correlate with moderate-severe chronic periodontitis susceptibility,but were associated with susceptibility to coronary heart disease particularly in the absence of other risk factors such as smoking,hypertension, hyperlipidema and alcohol drinking.Interleukin-1-511C/T and interleukin-6-572C/G. polymorphisms were potential risk factors for CHD in GuangDong Han population.