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Variation In The PPARα Gene (V227A) Associates With Dyslipidemia

Posted on:2009-05-02Degree:MasterType:Thesis
Country:ChinaCandidate:S Q WangFull Text:PDF
GTID:2144360245464949Subject:Internal Medicine
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Background It's well-known that dyslipidemia is important .Its mechanism has not yet been clarified. With the discovery of peroxisome proliferator-activated receptors , the association of peroxisome proliferator- activated receptor alpha(PPARα) with dyslipidemia is being received a lot of attention. Recent studies have shown that PPARαis widely expressed in all organs and tissues, such as liver, kidney, heart ,small intestine, and brown adipose tissue. PPARαregulates the transcription of key proteins involved in lipid metabolism, immunity response, cell differentiation ,as well as inflammatory reactions.In early 2002, Dr Yamakawa-kobayashi K screened 401 Japanese subjects (207men, 194women) and found allele frequencies for the A227 allele of 0.051.the presence of A227 was associated with lower serum concentrations of total cholesterol and triglycerides.In 2006,Dr. Edmund Chan ,Singapore General Hospital ,genotyped 4248 subjects (2899 Chinese, 761 Malay and 588 Asian Indians, all of which lived in Singapore ) ,and found the association between V227A polymorphism and serum lipid concentration in Chinese. Therefore, we study PPARαgene Val227Ala polymorphism and explore the association of peroxisome proliferator- activated receptor alpha(PPARα) gene V227A variation with dyslipidemia living in Dalian of China.Objective The purpose of this study by analyzing PPARαgene V227A polymorphism in Chinese living in Dalian is to explore the agreement of the mutation rate with what reported in oversea, and to explore the correlation of PPARαgene A227 variation with dyslipidemia.Methods Dylipidemia subjects( one of TC or TG is higher than normal at least ) are composed of 100 patients(58 men and 42 women) , a mean age (SD) of 53.48 (SD 13.14) years, and all of them is Han people of Dalian. Normal control subjects are composed of 100 patients (48 men and 52 women) ,diabetes and dyslipidemia are except , a mean age (SD) of 51.57 (SD 11.58) years. All the subjects selected are excepted for tumor, severe liver and kidney dysfunction ,cardia insufficiency and the prensence of stress factors. All of them are the Han people living in Dalian. Extracted peripheral blood white blood cell genomic DNA is to detect PPARαV227A polymorphism by the application of polymerase chain reaction-restriction fragment length polymorphism (PCR-PFLP), and calculate genetype and allele frequency of each group,as well as differences;simultaneously compare with body mass index (BMI), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), blood urea nitrogen (BUN), camine (CR), uric acid (UA), fasting blood glucose (FBG), glutamic pyruvic transaminase (GPT), glutamic oxalacetic transaminase (GOT) between the two groups.Results①The overall frequencies of VV, VA in normal control group subjects and in dylipidemia group subjects were 88%, 12%, and 99%, 1%, respectively. There was statistical difference in the genetype frequency distribution between the two groups by check-up (χ2=9.955 p<0.01 ). The V227 allele frequency is 94%, and A227 allele frequency is 6% in normal control subjects; and the V227 allele frequency is 99.5%, and A227 allele frequency is 0.5% in dyslipidemia subjects . There is no statistical difference between them by check-up (χ2=3.22 P>0.05).②the mean serum total cholesterol and triglyceride levels in carriers of the A227 allele were significantly lower than those in non-carriers.Conclusion The association of PPARαV227A gene polymorphism with dyslipidemia is evident in Dalian Chinese. In the normal control subjects A227 ellele frequency is more elevatory than the dyslipidemia subjects. A227 variation is possibly protective factor for dyslipidemia.And the variation rate is consistent with what reported abroad.
Keywords/Search Tags:peroxisome proliferator-activated receptor alpha(PPARα), dyslipidemia, PPARαV227A polymorphism
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