The Association Study On Common SNPs Of LIPC、CETP Gene And Hypertensive Disorders Complicating Pregnancy

【Objective】Our research aim to investigate if these polymorphisms (-250G/A(rs2070895)、-514C/T(rs1800588) in LIPC; TaqIB(rs708272) in CETP) is susceptibility traits ofhypertensive disorders complicating pregnancy (HDCP) and affect lipid metabolismof this disorder.【Methods】1. Totally652peripheral blood samples (321HDCP patients and331controls) in aChinese Han population in Fujian province were collected according to inclusionstandards and exclusion standards,2ml per sample. The full-set blood fat test resultsand other clinical data of them about first test were also collected.2. These data of3identified SNPs (-250G/A and-514C/T in LIPC gene, TaqIB inCETP gene) in NCBI SNP database were searched.3. Genomic DNA was extracted from peripheral blood samples;3pairs of SNPsprimers for amplification were designed; The SNP containing regions were amplifiedusing PCR.4. The amplified products were subjected to RFLP, these alleles’ frequencies andgenotype frequencies were counted.5. The relationship between each SNP and each blood-fat index was analyzed bySPSS13.0statistic software.6. SHEsis software were used for linkage disequilibrium tests and haplotype analysesof different locuses of LIPC gene polymorphism.【Results】1. The test of Hardy-Weinberg equilibrium showed that the two single nucleotidepolymorphism (SNP) sites (-250G/A,-514C/T) was in conformity with the geneticequilibrium and the other one (TaqIB) in HDCP diverged from the genetic equilibrium(P＜0.05).2. Allele frequences of three SNPs (-250G/A,-514C/T, TaqIB) as follows:G allele frequency distribution of-250G/A polymorphism in HDCP and controlswere0.609,0.603, respectively, A allele frequency distribution were0.391,0.397;C allele frequency distribution of-514C/T polymorphism in HDCP and controlswere0.632,0.622, respectively, T allele frequency distribution were0.368,0.378;B1allele frequency distribution of TaqIB polymorphism in HDCP and controlswere0.583,0.606, respectively, T allele frequency distribution were0.417,0.394.3. TG, TC, ApoA1, ApoB, HDL-C, BMI, SBP, DBP level among different genotypesof three SNPs are not statistically significant differences in HDCP group(P＞0.05).Research based on HDCP subgroup found that TG, TC level among differentgenotypes of TaqIB polymorphism are statistically significant differences in severepreeclampsia(SPE) group(F=3.45, P=0.03; F=3.76, P=0.02, respectively); BMI levelamong different genotypes of-250G/A polymorphism are statistically significantdifferences in mild preeclampsia(MPE) group(F=5.01, P=0.01);TC, SBP level amongdifferent genotypes of-250G/A polymorphism are statistically significant differencesin gestational hypertension(GH) group (F=9.75, P＜0.001; F=3.68，P=0.03,respectively), either in-514C/T polymorphism (F=10.58, P＜0.001; F=5.21，P=0.009,respectively).4. Through ANOVA test, HDL-C level among3genotypes in LIPC gene-250G/A issignificant differences (F=3.22, P=0.04), HDL-C level of A/A genotype is highest incontrols; TG,TC,ApoB level among various genotypes in CETP gene TaqIB issignificant differences (F=4.77, P=0.009; F=3.85, P=0.02; F=3.20, P=0.04,respectively), TG, TC, ApoB level of B2B2genotype are highest.5. Binary logistic regression analysis showed that BMI and serum lipids (TG, ApoA1and HDL-C) after adjusting other confounding factors, were significantly associatedwith occurrence of HDCP (P all＜0.05).6. Linkage disequlibrum was found between the two SNP sites (-250G/A,-514C/T) inthe promoter region of LIPC gene in HDCP(D’=0.98, r2=0.87).7. Frequencies of LIPC gene haplotypes: there are4haplotypes. Add up two figures(Hap*2, Hap*3), the frequence is about97%. Distribution of Hap*2and Hap*3in HDCP group are not statistically significant differences from control (P＞0.05)【Conclusion】LIPC-250G/A(rs2070895),-514C/T (rs1800588) and CETP TaqIB (rs708272)polymorphisms are not associated with HDCP；LIPC gene-250G/A、-514C/T polymorphism are significantly associated withTC, SBP level of GH patients, suggesting-250A and-514T are risk factors of raisedTC, SBP level in GH patients;-250G/A polymorphism is significantly associated withbody mass index (BMI) of MPE patients, suggesting-250AA genotype is dangerousgenotype of overweight in MPE patients; CETP gene TaqIB polymorphism issignificantly associated with TG, TC level in SPE patients, suggesting B2B2genotypeis risk genotype of raised TG, TC level in SPE patients.