| Objective:GWAS have identified a large cluster of genetic susceptibility regions associated with lipid metabolism,some of which were validated in different races.CELSR2,SORT1,PSRC1,HMGCR,LPL and LIPC in large-scale population studies found that not only involved in regulating lipid metabolism changes,may be associated with risk of cardiovascular disease risk.In this study,candidate SNPs was used as genetic markers and genotyped by the dye terminator-based SNaPshot method.Correlation analysis and risk assessment of dyslipidemia with 8 SNPs(CELSR2:rs599839;SORT1:rs4970834;PSRC1:rs646776;HMGCR:rs12654264,rs3846662;LPL:rs331,rs327;LIPC:rs1077834)in Chengdu community of Han population and susceptible candidate gene were conducted by continuous variables and case-control study model.Methods:Part 1.The epidemiological indicators of 1900 Han population were analyzed,including BMI,GLU,SBP,DBP,TC,TG,LDL-C and HDL-C.①age analysis:A total of 1900 patients were divided into two different age groups,aged 60 years(>60 years)and younger than 60 years(<60 years),and the association of BMI,blood GLU,SBP,DBP and serum lipid parameters(TC,TG,LDL-C HDL-C)level were compared by t test;all serum lipid parameters were divided into normal and abnormal groups according to the critical value of dyslipidemia,and the chi square test was using to compared between the two groups of serum lipid parameters.②gender analysis:A total of 1900 patients were divided into male group and female group,and the association of BMI,GLU,SBP,DBP and serum lipid parameters(TC,TG,LDL-C HDL-C)level were compared by t test;all serum lipid parameters were divided into normal and abnormal groups according to the critical value of dyslipidemia,and the chi square test was using to compared between the two groups of serum lipid parameters.Part 2:Analysis of candidate genes SNPs with serum lipid Components.①The relationship between serum lipid parameters level and candidate SNPs of total study population level was analyzed.② SNPs associated with serum lipid parameters level in total study population were further divided into two different age groups,aged 60 years(>60 years)and younger than 60 years(<60 years),and then analysis the correlation with serum lipid parameters level by using case-control study;③ SNPs associated with serum lipid parameters level in total study population were further divided into male group and female group.Part 3:Logistic regression was used to analyze the risk of dyslipidemia(One of TC,TG,LDL-C and HDL-C is abnormal)and candidate SNPs.①The univariate logistic regression was used to analyze the association between dyslipidemia and SNPs,further the risk assessment was carried out by multivariate logistic regression.②The SNPs which associated with dyslipidemia were divided into male and female groups,and risk assessment was performed for both groups.Results:Part 1:In this study,there were 1,900 subjects,including 746 males,aged 60.06 ± 13.21 years,and 1154 females,aged 59.61 ± 10.85 years;BMI 23.98±3.16 kg/m2,GLU 5.25±1.51 mmol/L,SBP 129±19.7 mmHg,DBP 78±10.9 mmHg,TC 5.22±0.93 mmol/L,TG 1.59±1.38,LDL-C 3.14±0.86,HDL-C 1.35±0.31;TC:normal 978(61%),abnormal 625(39%);TG:normal 1361(71.6%),abnormal 539(28.4%);LDL-C:normal 1242(65.4%),abnormal 658(34.6%);HDL-C:normal 1622(85.4%),abnormal 278(14.6%).①T test analysis shows:there was a significant association in BMI,GLU,SBP,blood DBP,TC,LDL-C and HDL-C between age groups(p≤0.05);GLU,SBP,DBP,TC and LDL-C means of low age group(<60 year)lower than the high age group(≥60 year),HDL-C means of high age group(≥60 year)lower than the low age group(<60 year),while BMI and TG have no significant association between the two groups(p>0.05).The chi-square test shows:there was a significant association between the normal and abnormal groups of lipid parameters in the age groups(p<0.05).②T test analysis shows:there was a significant association in BMI,GLU,SBP,DBP,TC,LDL-C and HDL-C between the male and female groups(p<0.05);BMI,GLU,SBP,DBP and TG means of female group lower than the male group,TC and HDL-C means of male group lower than the female group,while LDL-C have no significant association between the two groups(p>0.05).The chi-square test shows:there was a significant association between the normal and abnormal groups of lipid parameters in the male and female groups(p<0.05).Part 2:Candidate SNPs and serum lipid parameters level association analysis shows:①The total population:the level of serum TC significant associate with the allele of rs599839(p=3.7×10-4),rs646776(p=0.001),rs12654264(p=1.4×10-5)and rs3846662(p=9.9×10-5);the level of serum LDL-C significant associate with the allele of rs4970834(p=4.49×10-4),rs599839(p=1.5×10-5),rs646776(p=3.5×10-5),rs12654264(p=0.001)and rs3846662(P=0.001);the level of serum HDL-C significant associate with the allele of rs327(p=0.001),rs331(p=1.19×10-4)and rs1077834(p=0.004);the level of serum TG have no significant associate with the allele of candidate SNPs.②the low age group(<60 years):the level of serum TC significant associate with the allele of rsl2654264(p=2.9×10-5)and rs3846662(p=1.7×10-5),while have no significant association with rs646776 and rs599839(p>0.05);the level of serum LDL-C significant associate with the allele of rs599839(p=3.5×10-4),rs646774(p=0.001),rs12654264(p=3.6×10-4)and rs3846662(p=5.3×10-5),while have no significant association with rs4970834(p>0.05);the level of serum HDL-C significant associate with the allele of rs331(p=1.7×10-5),while have no significant association with rs327 and rs1077834(p>0.05).The high age group(≥ 60 years):the level of serum TC significant associate with the allele of rs599839(p=0.003)and rs646774(p=0.004),while have no significant association with rs12654264 and rs3846662 alleles(p>0.05);The level of serum LDL-C significant associate with the allele of rs4970834(p=0.003),rs599839(p=0.004)and rs646774(p=0.005),while have no significant association with rs12654264 and rs3846662 alleles(p>0.05);There was no significant association in the serum levels of HDL-C with rs327,rs331 and rs1077834 alleles(P>0.05).③The male group:The level of serum LDL-C significant associate with the allele of rs327(p=0.003)and rs331(p=0.002),while have no significant association with rs 1077834 alleles(p>0.05);There was no significant association in the serum levels of TC and HDL-C with SNPs.The female group:The level of serum TC significant associate with the allele of rs599839(p=0.001),rs646776(p=0.001),rs12654264(p=8.6×10-5)and rs3846662(p=0.002);The level of serum LDL-C significant associate with the allele of rs4970834(p=0.006),rs599839(p=1.83×10-4),rs646776(p=3.34×10-4),rs12654264(p=0.002)and rs3846662(p=0.003);There was no significant association in the serum levels of HDL-C with rs327,rs331 and rs1077834(p>0.05).Part 3:Multivariate logistic regression analysis shows:①The total population:The minor alleles of rs599839(p=0.019,OR=0.692,95%CI:0.509-0.941)and rs12654264(p=0.009,OR=0.815,95%CI:0.700-0.949)were associated with lower concentrations of TC;The minor alleles of rs4970834(p=0.004,OR=0.510,95%CI:0.323-0.805),rs599839(p=3.2×10-4,OR=0.532,95%CI:0.378-0.750),rs646776(p=0.009,OR=0.623,95%CI:0.436-0.889),rs12654264(p=0.001,OR=0.753,95%CI:0.642-0.884)and rs3846662(p=0.001,OR=0.755,95%CI:0.640-0.892)were associated with lower concentrations of LDL-C;The minor alleles of rs331(p=0.014,OR=0.747,95%CI:0.592-0.943)were associated with lower concentrations of TC;There was no significant association between dyslipidemia with rs327 and rs1077834(p>0.05);②The male group:The minor alleles of rs4970834(p=0.027,OR=0.387,95%CI:0.167-0.900)and rs331(p=0.030,OR=0.654,95%CI:0.446-0.959)were associated with lower concentrations of LDL-C;There was no significant association between dyslipidemia with rs599839 and rs646776(p>0.05).The female group:The minor alleles of rs599839(p=0.002,OR=0.509,95%CI:0.333-0.780),rs646776(p=0.018,OR=0.579,95%CI:0.369-0.909),rs12654264(p=0.005,OR=0.751,95%CI:0.616-0.917)and rs3846662(p=0.021,OR=0.782,95%CI:0.635-0.963)were associated with lower concentrations of LDL-C;The minor alleles of rs12654264(p=0.016,OR=0.788,95%CI:0.650-0.956)was associated with lower concentrations of TC;There was no significant association between dyslipidemia with rs4970834 and rs331(p>0.05).Conclusion:1.The SNPs of candidate genes(CELSR2:rs4970834,SORT1:rs646776,PSRC1:rs599839,HMGCR:rs12654264 and rs3846662,LPL:rs327 and rs331,LIPC:rs1077834)were associated with one or more lipid parameters in Chengdu community of Han population,in which the alleles of rs4970834 was significant associated with serum LDL-C level in the higher age group(≥60 year)and female group;the alleles of rs599839 and rs646774 were significant associated with serum LDL-C level in the higher age group(>60 year)and female group,and also significant associated with serum TC level in the higher age group(≥60 year)and female group;The alleles of rs12654264 and rs3846662 were significant associated with serum LDL-C and TC level in the younger group(<60 years)and female group;The alleles of rs327 was significant associated with serum HDL-C level in male group;The alleles of rs331 was significant associated with serum HDL-C level in the younger group(<60 years)and male group.2.PSRC1(rs599839)and HMGCR(rs12654264,rs3846662)significantly influence the risk of dyslipidemia,that the minor allele of rs3846662(T)can reduce the risk of higher LDL-C level in man;the minor allele of rs12654264(A)and rs599839(G)can reduce the risk of higher LDL-C levels in women. |
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