| Objective: 1.To detect the association between rs2230806,rs4149313,rs2275542,rs2515602,rs3890182,rs1800976 polymorphisms in ABCA1 gene and low HDL-C disease in Uygurs and Kazakhs.2.Analysis the interactions for rs2230806,rs4149313,rs2275542,rs2515602,rs3890182,rs1800976 polymorphisms in ABCA1 gene and environments as well as the interactions among the six locis in Uygurs and Kazakhs with low HDL-C disease.3.Analysis the relationships between rs2230806,rs4149313,rs2275542,rs2515602,rs3890182,rs1800976 polymorphisms in ABCA1 gene and serum lipids in Uygurs and Kazakhs.4.To investgate that whether there is a linkage disequilibrium of rs2230806,rs4149313,rs2275542,rs2515602,rs3890182,rs1800976 polymorphisms in ABCA1 gene and relathionships between their halotypes and low HDL-C disease in Uygurs and Kazakhs.Methods: 1.For Kazakhs,a total of 204 patients with low HDL-C and 207 health control subjects,which were randomly selected from the data we established before;For Uygurs,randomized sampling 263 patients with low HDL-C and 275 health control subjects from the data we collected before;2.We genotyped ABCA1 single nucleotide polymorphisms of rs2515602,rs3890182,rs2275542,rs2230806,rs1800976,and rs4149313 by using the SNa Pshot;3.Data processing were used with SPSS 20.0 statistical package,Statistical analysis methods including ?2 test,the Student's t-Test,univariate and multivariate analysis using Logistic regression analysis.Interactions between six SNPs in ABCA1 gene and environments were assessed by using unconditioned Logistic regression analysis,gene-gene interactions were analyzed by multifactor dimensionality reduction(MDR software),and SHEsis online software was used to analysis haplotype and linkage disequilibrium.Results: 1.For Kazakhs,the genotypic and allelic frequencies of rs2515602,rs2230806 and rs4149313 were different between the control group and the case group(p < 0.05).For rs2515602 polymorphism,we observed a higher frequency of the C allele(60.8% VS 43.9,p < 0.001)in low HDL-C patients compared with control group.For rs2230806 polymorphism,we observed a lower frequency of the A allele(31.2% vs 45.6%,p < 0.001)in control group compared with case group.For rs4149313 polymorphism,we observed a higher frequency of the A allele(68.1% vs 54.4%,p < 0.001)in control group compared with case group;2.For Kazakhs,rs3890182,rs2275542 and rs1800976 polymorphisms were not associated with lipid levels(all p >0.017).rs2515602 with CC genotype has lower HDL-C level than in with CT/TT genotype,CT genotype has lower HDL-C level than in with TT genotype,and TT genotype has higher TC than in with CC genotype(p < 0.017);Serum HDL-C level was lower according to rs2230806 with AA genotypethan in GGgenotype(p < 0.017);Serum HDL-C level was higher according to rs4149313 with AA genotype than in AG/GG genotype(p < 0.017),The level of TC was higher with AA genotype than in with GG genotype for rs4149313(p < 0.017);3.Obesity(OR = 1.460;95% CI: 1.185-1.797;p < 0.001),rs2516602(OR = 1.666;95% CI: 1.115-2.488;p = 0.013)and rs4149313(OR = 1.722;95% CI: 1.152-2.572;p = 0.008)polymorphisms are independent risk factors for low HDL-C in Kazakhs;the low HDL-C disease might partly result from interactions between rs4149313 in ABCA1 gene polymorphisms and obesity(OR = 1.753;95% CI: 1.171-2.624;p = 0.006);4.Multifactor dimensionality reduction analysis results show that the combination effect of rs2515602 and rs2275542 model is the most optimal interaction model in Kazakhs(p = 0.0107),and this model shows antagonistic action;the interactions among rs2515602,rs2275542 and rs1800976 also show a significant effect on low HDL-C disease(p = 0.0107);5.For Kazakhs,strong linkage disequilibrium was noted between rs2230806 with rs2515602(D' = 0.821),and rs4149313 with rs2515602(D' = 1);6.ABCA1 6 locis in Kazakhs constructed 36 haplotype species.C-C-G-A-G-G?T-T-T-G-G-A?C-C-C-A-G-G ? C-C-G-G-G-G ? C-C-G-A-G-A ? T-C-C-G-G-G ? T-C-C-A-G-G ? T-C-C-A-G-A,and T-T-C-G-G-A haplotype frequencies differences between the case group and the control group was statistically significant(p <0.05).7.For Uygurs,the genotypic and allelic frequencies of rs2515602,rs2230806 and rs4149313 were different between the control group and the case group(p < 0.05).For rs2515602 polymorphism,we observed a higher frequency of the C allele(59.1% vs 52.4,p = 0.026)in low HDL-C patients compared with control group.For rs2230806 polymorphism,we observed a lower frequency of the A allele(32.4% vs 39.4%,p = 0.017)in control group compared with case group.For rs4149313 polymorphism,we observed a higher frequency of the A allele(64.4% vs 52.7%,p < 0.001)in control group compared with case group;8.For Uygurs,rs3890182?rs2275542 and rs2230806 polymorphisms were not associated with lipid levels(all p >0.017).rs2515602 with TT genotype has lower TG level than in with CT/TT genotype(p < 0.017);Serum TG?TC and LDL-C levels were lower according to rs1800976 with GG genotype than in CG genotype(p < 0.017);Serum TG level was higher according to rs4149313 with GG genotype than in AA genotype(p < 0.017),The level of HDL-C was higher with AA genotype than in with GG genotype for rs4149313(p < 0.017);9.Obesity(OR = 1.235;95% CI: 1.102-1.384;p < 0.001),hypertension(OR = 1.316;95% CI: 1.102-1.573;p = 0.002)and rs4149313(OR = 1.718;95% CI: 1.238-2.385;p = 0.001)polymorphisms are independent risk factors whereas female(OR = 0.383;95% CI: 0.257-0.571;p < 0.001)may serve as protective factor of low HDL-C disease among Uygurs;the low HDL-C disease might partly result from interactions between rs4149313 in ABCA1 gene polymorphisms and obesity(OR = 1.556;95% CI: 1.247-1.941;p < 0.001)?sex(OR = 1.542;95% CI: 1.070-2.223;p = 0.02)?hypertension(OR = 1.334;95% CI: 1.131 – 1.573;p < 0.001);10.Multifactor dimensionality reduction analysis results show that the combination effect of rs4149313 and rs1800976 model is the most optimal interaction model in Uygurs(p = 0.0010),and this model shows synergistic action;the interactions among rs2230806,rs1800976 and rs4149313 also show a significant effect on low HDL-C disease(p = 0.0010);11.For Uygurs,strong linkage disequilibrium was noted between rs2275542 with rs3890182(D' = 0.801),rs2515602 with rs2230806(D'= 0.870)?rs3890182(D' = 0.741)?rs4149313(D' = 1);12.ABCA1 six locis in Uygurs constructed 39 haplotype species.C-T-G-G-G-A?C-C-C-A-G-G?T-C-G-G-G-G?T-C-G-A-G-G?T-C-G-A-G-A,and T-T-C-G-G-A haplotype frequencies differences between the case group and the control group was statistically significant(p <0.05).Conclusions: 1.There was a significant relationship between rs2515602,rs2275542,rs2230806 and rs4149313 polymorphisms in ABCA1 gene and low HDL-C disease in Kazakhs.rs2515602-T allele,rs2230806-G allele may be protective factors of low HDL-C disease,however,rs4149313-G allele and rs2275542-CT may be risk factors of low HDL-C disease;2.The levels of HDL-C(rs2515602,rs4149313 and rs2230806)and TC(rs2515602 and rs4149313)were different among the genotypes.3.Obesity,rs2516602 and rs4149313 polymorphisms are independent risk factors for low HDL-C in Kazakhs;the low HDL-C disease might partly result from interactions between rs4149313 in ABCA1 gene polymorphisms and obesity;4.Multifactor dimensionality reduction analysis results show that the combination effect of rs2515602 and rs2275542 model is the most optimal interaction model in Kazakhs,and this model shows antagonistic action;the interactions among rs2515602,rs2275542 and rs1800976 also show a significant effect on low HDL-C disease;5.Strong linkage disequilibrium was noted between rs2230806 with rs2515602 and rs2515602 with rs4149313.6.The C-C-G-A-G-G?T-T-T-G-G-A?C-C-C-A-G-G?C-C-G-G-G-G?C-C-G-A-G-A?T-C-C-G-G-G?T-C-C-A-G-G?T-C-C-A-G-A haplotypes may serve as risk factors of low HDL-C disease among Kazakhs,the T-T-C-G-G-A haplotype may serve as protective factor of low HDL-C disease among Kazakhs.7.There was a significant relationship between rs2515602?rs2230806 and rs4149313 polymorphisms in ABCA1 gene and low HDL-C disease in Uygurs.rs2515602-T allele?rs2230806-G allele may be protective factors of low HDL-C disease,however,rs4149313-G allele may be risk factors of low HDL-C disease;8.The levels of HDL-C(rs4149313),LDL-C(rs1800976),TG(rs1800976,rs2515602 and rs4149313),and TC(rs1800976)were different among the genotypes in Uygurs.9.Obesity,male,hypertension and rs4149313 polymorphism are independent risk factors for low HDL-C in Uygurs;the low HDL-C disease might partly result from interactions between rs4149313 in ABCA1 gene polymorphisms and obesity,sex,hypertension;10.Multifactor dimensionality reduction analysis results show that the combination effect of rs4149313 and rs1800976 model is the most optimal interaction model in Uygurs,and this model shows synergistic action;the interactions among rs2230806,rs1800976 and rs4149313 also show a significant effect on low HDL-C disease;11.For Uygurs,strong linkage disequilibrium was noted between rs2275542 with rs3890182,rs2515602 with rs2230806?rs3890182?rs4149313;12.The C-C-C-A-G-G,T-C-G-G-G-G,and T-C-G-A-G-G haplotypes may serve as risk factors of low HDL-C disease among Uygurs;the T-C-G-A-G-A haplotype may serve as protective factor of low HDL-C disease among Uygurs. |
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