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Study On The Association Of Single Nucleotide Polymorphisms In PPARa Gene And Amp1 Gene With Coronary Heart Disease And Type 2 Diabetes

Posted on:2009-12-07Degree:MasterType:Thesis
Country:ChinaCandidate:X X ChenFull Text:PDF
GTID:2144360245977430Subject:Cell biology
Abstract/Summary:PDF Full Text Request
Objective: Many epidemiological studies and reviews have demonstrated that dyslipidemia was associated with heterogeneity of the onset and severity of coronary heart disease (CHD), in addition, it is also a clinical feature of type 2 diabetes mellitus (T2DM), and then it has been proposed to be a risk factor for T2DM. The purpose of this study was to evaluate the influence of variants in the lipid metabolism related genes peroxisome proliferators-activated receptor-a(PPARa),apM1 on the risk of developing CHD and T2DM and the effect between the two genes interaction CHD and T2DM. These variants were -12601A>C and -20337A>G polymorphisms in the PPARa gene,-3971 A>G and +4544 C>G polymorphisms in apM1 gene.Methods: We examined these four single nucleotide polymorphisms (SNPs)( -12601A>C and -20337A>G polymorphisms in the PPARa gene, -3971A>G and C4544G polymorphisms in the apM1 gene) in 369 patients with CHD,401 patients with T2DM and in 339 controls by PCR-RFLP. Then,we analysed the association of these SNPs with lipid metabolism in patients with CHD,T2DM and controls. Case-control comparisons were performed separately for CHD,T2DM and controls by using SPSS statistical software package.Results: 1.No significant difference of allelic or genotypic frequencies either of -12601A>C polymorphism in PPARa gene between the CHD,T2DM patient and control subjects were observed.The value of TG in homozygous A/A of the CHD is lower in homozygous C/C of the CHD(A/AVSA/C,q=3.9644,P<0.05). The value of TC in homozygous A/A of the CHD is lower in heterozygote A/C of the CHD and in homozygous C/C of the CHD(A/AVSA/C,q=7.88,P<0.01;A/AVSC/C,q=4.2867,P<0.01) . The value of TG in homozygous A/A of the T2DM is lower in heterozygote A/C of the CHD and in homozygous C/C of the (A/AVSA/C,q=3.1570,P<0.05;A/AVSC/C,q=4.2867,P<0.01)2. No significant difference of allelic or genotypic frequencies either of -20337A>G polymorphism in PPARa gene between the CHD, T2DM patient and control subjects were observed.The value of TG in homozygous A/A of the CHD is lower in heterozygote A/G of the CHD and in homozygous G/G of the CHD (A/AVSA/G,q=4.5245,P<0.01;A/AVSG/G,q=5.2867,P<0.01). The value of TG in homozygous A/A of the T2DM is lower in heterozygote A/G of the T2DM and in homozygous G/G of the CHD (A/AVSA/G,q=3.6986,P<0.05;A/AVSG/G,q=2.9384,P<0.05). The value of HDL-C in homozygous A/A of theT2DM is higher in heterozygote A/C of the T2DM and in homozygous G/G of the T2DM ((A/AVSA/G,q=3.157,P<0.05;A/AVSG/G,q=3.7857,P<0.05)) . The value of TG in heterozygote A/G of the controls is higher in homozygous G/G of the controls (A/GVSG/G,q=3.5954,P<0.05).3.No significant difference of allelic or genotypic frequencies either of -3971A>G polymorphism in apM1 gene between the CHD, T2DM patient and control subjects were observed.The value of TG in homozygous A/A of the CHD is lower in heterozygote A/G of the CHD and in homozygous G/G of the CHD (A/AVSA/G,q=3.9644,P<0.05 ;A/AVSG/G,q=4.2867,P<0.01). The value of LDL-C in homozygous A/A of the CHD is lower in heterozygote A/G of the CHD and in homozygous G/G of the CHD ((A/AVSA/G,q=7.88,P<0.01;A/AVSG/G,q=4.2867,P<0.01)。The value of TG in homozygous A/A of the T2DM is higher in heterozygote A/C of the CHD and in homozygous G/G of the T2DM (A/AVSA/G,q=3.5242,P<0.05 ;A/AVSG/G,q=3.5813,P<0.05). 4. No significant difference of allelic or genotypic frequencies either of +4544C>G polymorphism in apM1 gene between the CHD patient and control subjects were observed. No significant difference of genotypic frequencies either of +4544C>G polymorphism in apM1 gene between the T2DM patient and control subjects were observed.There is significant difference of allelic frequencies either of +4544C>G polymorphism in apM1 gene between the T2DM patient and control subjects were observed. The value of TG in homozygous C/C of the CHD is lower in heterozygote C/G of the CHD and in homozygous G/G of the CHD (C/CVSC/G,q=7.1224,P<0.01 ;C/CVSG/G,q=3.5441,P<0.05). The value of LDL-C in homozygous C/G of the CHD is lower in heterozygote C/G of the CHD and in homozygous G/G of the CHD (C/CVSC/G,q=3.6986,P<0.05;C/CVSG/G,q=2.9384,P<0.05). The value of TG in homozygous G/G of the controls is higher in heterozygote C/G of the CHD and in homozygous C/C of the controls (G/GVSC/C,q=3.4038,P<0.05; G/GVSC/G,q=4.3349,P<0.01).5.Significant difference of genotypic frequencies of -3971A>G polymorphism in apM1 gene between the T2DM patient and control subjects in hypotype of A/C in -12601bp PPARagene were observed(x2=11.2, P<0.05)and significant difference of genotypic frequencies of -3971A>G polymorphism in apM1 gene between the T2DM patient and control subjects in hypotype of C/C in -12601bp PPARagene were observed(x2=10.3. P<0.05).Significant difference of genotypic frequencies of +4544C>G polymorphism in apM1 gene between the CHD patient,T2DM patient and control subjects in hypotype of A/C in -12601bp PPARagene were observed(x2=20.9, P<0.05; x2=12.5, P<0.05).Significant difference of genotypic frequencies of -3971A>G polymorphism in apM1 gene between the CHD patient and control subjects in hypotype of G/G in -20337bp PPARagene were observed(x2=6.18, P<0.05).Significant difference of genotypic frequencies of + 4544C>G polymorphism in apM1 gene between the CHD patient and control subjects in hypotype of A/A in -20337bp PPARagene were observed(x2=13.4, P<0.05)and significant difference of genotypic frequencies of +4544C>G polymorphism in apM1 gene between the CHD patient,the NIDDM patient and control subjects in hypotype of C/C in -20337bp PPARagene were observed(x2=16.6,P<0.05; x2=7.65,P<0.05).Conclusion:Our investigation provided the evidence that the association is found between the apM1+4544C>G polymorphism and CHD , There is no significant correlation between the PPARa -12601A>C polymorphism,PPARa-20337A>G polymorphism,apM1-3971A>G polymorphism and CHD. There is no significant correlation between the PPARa -12601A>C polymorphism,PPARa-20337A>G polymorphism,apM1-3971A>G polymorphism apM1+4544C>G and T2DM . There is significant correlation between the PPARa -12601A>C polymorphism,PPARa-20337A>G polymorphism,apM1-3971A>G polymorphism apM1+4544C>G and blood fat in CHD group and T2DM group . The synergistic effect of PPARa gene and apM1gene has an effect on CHD and T2DM.
Keywords/Search Tags:peroxisome proliferators-activated receptor-a(PPARa), apM1, single nucleotide polymorphism, coronary heart disease, type 2 diabetes mellitus
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