Correlation Between PCSK9and LDLR Gene Polymorphism, Behavioral Factors And Hyperlipidemia

Objective: The study is to detected the frequencies of8SNPs located on PCSK9and LDLR genes withpeople in Yinzhou District, Ningbo City, Zhejiang Province, analyzed the association betweenthe SNPs and hyperlipidemia and evaluated the gene-gene interaction and gene-environmentinteraction on hyperlipidemia. It was to provide basic information of the individual prevention andcontrol for hyperlipemia．Methods:2303subjects in over the age of40were selected from the Yinzhou District, Ningbo City,Zhejiang Province, and divided in to case (771) and control (1532). Measuring their body weight, waistcircumference, blood pressure and other indicators. Peripheral blood samples were drawn from eachsubject with informed consent8SNPs of PCSK9and LDLR gene were analyzed by ligase detectionreaction.All the calculations and statistics were performed with the computer program, SPSS version17.0.Statistical analysis adopt t test,ANOVA，χ2test and one-way logistic regression. Linkage disequilibriumwas analyzed by Haploview software Haplotype analysis was estimated by Haplo.stats package of Rsoftware. Crossover analysis were applied to explore interactive effects of the genetic polymorphisms andlife behavior factors on hyperlipidaemia risk.Results:(1) All the clinical and biochemical index in the cases were significantly higher than that in thecontrol except plasma HDL-C and height (P <0.05).(2) Frequencies of each genotype did not indicatedeviations form Hardy-Weinberg equilibrium (P>0.05).(3) HDL-C levels of GG carriers weresignificantly lower than AA+AG carriers in rs2738466，TC and LDL-C levels of CC carriers weresignificantly lower than CT+TT carriers in rs1003723, TC and LDL-C levels of AA carriers weresignificantly lower than AG+GG carriers in rsrs6413504.(4) No significant difference in frequencybetween hyperlipemia group and control group was located among genotypes of PCSK9and rs1003723,rs6413504of LDLR gene respectively（P>0.05). The differences genotype frequencies at rs2483205werestatistically significant（P<0.05).(5) Unconditional univariate logistic regression analysis showed that thehomozygous genotype of LDLR rs2738466exhibited a significantly increased risk of hyperlipemia afteradjusted for age (OR=1.40，95%CI=1.08~1.82). Unconditinal multiple logistic regression analysis showedthat these factors which rs662145, rs2738466, rs6413504, BMI, waist circumference, SBP, physical activityand alcohol were associate with hyperlipemia (OR=1.42,95%CI=1.11~1.81; OR=1.27,95%CI=1.04~1.55; OR=1.30,95%CI=1.08~1.58; OR=1.68,95%CI=1.42~1.99; OR=1.33,95%CI=1.07~1.65;OR=1.50,95%CI=1.24~1.82; OR=0.85,95%CI=0.75~0.96; OR=0.58,95%CI=0.46~0.73).(6) Nosignificant association was observed between PCSK9haplotypes and hyperlipemia risk. The haplotype GCof LDLR was associated with hyperlipemia.(7) BMI might be interaction between rs662145andrs2738466and rs6413504respectively, rs2738466and rs6413504might be interaction with rs662145respectively (Pinteraction<0.05).Conclusionas: It had lower HDL-C levels that minor allele of LDLR at rs1558861, it had higher TC andLDL-C levels that minor allele of LDLR at rs1003723and rs6413504. It could increased the risk ofhyperlipemia which genotype CT+TT of PCSK9rs662145, genotype AG+GG of LDLR rs2738466andrs6413504, obesity and SBP elevated. It could reduce the risk of hyperlipemia that physical activity. Thehaplotype GC of LDLR could increased the risk of hyperlipemia.