Association Between FGF23 Genetic Polymorphisms And Coronary Heart Disease

Background and ObjectiveFibroblast growth factor 23(FGF23)is gradually considered to be a nontraditional risk factor for coronary heart disease.The FGF23 gene polymorphisms are also proved to be related with FGF23 concentration and physiological function.However,no studies have investigated whether FGF23 gene variations are risk factors of coronary heart disease.An case-control study was performed in Chongqing Han population to explore the association between FGF23 genetic polymorphisms and Coronary Heart Disease.Method1.The samples were selected in the Department of Cardiology,Third Affiliated Hospital,Third Military Medical University between May 2014 and March 2015.All the subjects were unrelated Chongqing Han population and had been examined by coronary angiography.A total of 431 subjects including 231 CHD patients and 200 non-CHD subjects were finally enrolled in this clinical study.2.Data including age,smoking,drinking,drug use,previous medical history,and family history were collected using a questionnaire.The subjects’ height and weight were measured,and the body-mass index(BMI)was calculated.The sitting blood pressure at the upper arm was measured using a calibrated mercury sphygmomanometer.The hepatic function,renal function,blood glucose,lipid,insulin,C peptide and insulin were measured with the help of clinical laboratory.The comparison of these clinical data between the CHD and control groups was performed using the SPSS 18.0 software.3.We use DNA extraction kit DP-332 to extract DNA from blood samples.The Sequenom Massarray system was used for the genotyping of three FGF23 gene Tag single-nucleotide polymorphisms,namely rs7955866,rs13312756,and rs3812822.Chi-square(χ2)test or Fisher’s exact test was used for the Hardy-Weinberg equilibrium test in each SNP for patients in control group.And then,the SPSS 18.0 software was used to perform the comparison of the genotyping results between the CHD and control.Results1.The statistical results showed no significant differences in age,BMI,alcoholic intake,systolic blood pressure,diastolic blood pressure,and fasting C peptide between the CHD and case groups(P > 0.05).However,significant differences in the history of hypertension,smoking,family history of cardiovascular diseases,TC,TG,HDL-C,LDL-C,ApoA1,ApoB,Hb A1 c,FPG,2h PBG,and INS were found between the CHD and control groups(P < 0.05).And ROC curve analysis showed that the area under ROC curve of 2hPBG and INS were greater than fasting plasma glucose.2.The frequencies of rs7955866 A and rs3812822 C alleles in CHD group were significantly higher than in control group(P<0.001),and the distribution of the genotypes was also different between the two groups(P<0.01).Univariate Logistic regression analysis showed that the risk of developing CHD in the subjects carrying rs7955866 GA genotype was 2.146-fold of the ones carrying GG genotype(P=0.01,OR=2.146,95%CI:1.393-3.306),and rs3812822 CT genotype carriers also had a higher risk compared with the ones with TT genotype(P= 0.01,OR=2.010,95%CI:1.327-3.046).Adjusting for the confounding factors just like gender,age,BMI,smoking history,drinking history,history of hypertension and hypercholesterolemia.the results showed that the SNPs at rs7955866(P<0.001,OR=2.478,95%CI:1.613-3.806)and rs3812822(P<0.001,OR=2.123,95%CI:1.439-3.132)were independently associated with the development of CHD.The ACC Haplotype consisted by rs7955866-rs13312756-rs3812822 was also shown to have an effect on increasing CHD risk(P<0.001;OR=2.074,95%CI:1.391-3.091).Conclusion1.The FGF23 Gene is a susceptible gene of coronary heart disease in the Chongqing Han population.The single-nucleotide polymorphisms,namely rs7955866 and rs3812822,are independent risk factors for CHD.The ACC Haplotype consisted by rs7955866-rs13312756-rs3812822 was also shown to have an effect on increasing CHD risk.2.INS and 2hPBG are likely to be more important than FPG in the precaution of CHD,this means that it is necessary to examine INS and carry on OGTT experiment in the CHD risk screening.