| At present, insulin resistance andβcell deficiency are the basic pathogenesis of type 2 diabetes mellitus(T2DM). Insulin resistance may be the major factor. Macrovascular complications may contribute to the principal causes of morbidity and mortality in T2DM. Atherosclerosis (AS) is the pathogenic base of macroangiopathy. Insulin resistance, lipid metabolic dysfunction and hypertension are the main dangerous factors in AS. Peroxisome proliferator activated receptor(PPAR) is ligand-dependent transcription factors. PPARγ plays a crucial role in adipocytes differentiation. It can increase the formation of small adipocytes which are sensitive to insulin. Binding to synthetic ligand—thiazolidinedione(TZD), it can improve insulin resistance, decrease blood glucose level, lower the thickness of common carotid arterial intima and play an important role in anti-inflammation. PPARγ may promote AS by stimulating the uptake of oxidized LDL, and playing an important role in foam cell formation. On the other hand, Miles et al. found that in high fat diet, mice heterozygous for PPARγ deficiency improved insulin sensitivity not only in peripheral tissues but also in liver. Yamauchi et al. found PPARγ functional antagonist prevented rats from obesity and T2DM. Nevertheless, lowering its activity can increase insulin sensitivity and prevent T2DM and AS. The PPARγ gives rise to PPARγ1 and PPARγ2 by different promoter usage and different splicing. Yen et al. found a missense mutation(Pro→Ala) at codon 12 of PPARγ2 exon B by screening for mutations in the entire coding region of PPARγ gene. This variant lowers transcription capacity. It was found that people who had Ala allele protected against T2DM, increased insulin sensitivity and protected from coronary heart disease. But others found that there was no association between Pro12Ala variant and T2DM, as well as AS. The objective of our study is to investigate the association of PPARγ2 gene polymorphism with T2DM and early occurring AS in Han people of DaLian Chinese.Method According to WHO 1999 criteria, 202 type 2 diabetic patients newly diagnosed or with the duration under one year were selected. They are all Han people of DaLian Chinese. According to arterial intima-media thickness (IMT) measured by color doppler ultrasonography , we divided 202 cases into two groups: one group were 77 cases with AS(AS group)in which one of the carotid artery, common-iliac artery or femoral artery IMT was thicker than 1.0 millimeter or with localized blocks and the other were 125 cases without AS(non-AS group) in which all the above arteries IMT were thinner than 1.0 millimeter. The average age of AS group(42men and 35women) was 52.84 ±7.84 years. The average age of non-AS group (65men and 60women) was 51.90±7.70 years. The average age of 102 controls (without Diabetes Mellitus, hypertension, Diabetes Mellitus and hypertension family history, 59men and 43 women) was 57.58±12.33 years. All of them had not AS diseases, including heart, brain, kidney ,when they were selected. The genotypes of Pro12Ala variant in PPARγ2 gene exon B were determined by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) assay. The frequencies of PPARγ2-Pro12Ala genotype and allele gene were compared among them. In each group, body mass index (BMI), waist to hip ratio, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-Ch), low density lipoprotein cholesterol (LDL-Ch), insulin sensitivity index (ISI), glycosylated hemoglobin A1C (HbA1C) and C-reactive protein (CRP) were compared between Pro/Pro subgroup and Pro/Ala subgroup.Result The frequencies of Pro/Pro, Pro/Ala and Ala/Ala genotypes of PPARγ2 gene are 0.911,0.089 and 0 respectively; The frequencies of Pro allele and Ala allele are 0.956 and 0.044 in Han people of DaLian Chinese. The frequencies of Pro/Pro are not different between subjects in control group and diabetes(=0.687, P=0.407).There is no d... |
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