ABSTRACT
[Objective]To study the association of CAV1/CAV2 gene polymorphisms with type 2 diabetes in Chinese Han population.[Methods]14 single nucleotide polymorphisms(SNPs)of CAV1/CAV2 gene were genotyped in 272 pa-tients with type 2 diabetes mellitus(T2DM group)and 287 subjects with normal glucose tolerance(control group)by ma-trix-assisted laser desorption ionization-time of flight-mass spectrometry(MALDI-TOF-MS).Waist circumference,body mass index,plasma glucose,serum insulin and lipid profiles were measured.Homeostatic model assessment of insulin resis-tance(HOMA-IR)and β-cell function(HOMA-β)were calculated.[Results]The minor allele frequency(MAF)distri-butions of CAV1 rs926198,CAV2 rs2270188,and rs1052990 were significantly different between T2DM group and con-trol group(P=0.008,0.021,and 0.045,respectively). After adjusting for age,gender,and BMI,logistic regression analysis showed that minor allele carriers(CC/CT genotype)of CAV1 rs926198 displayed a particularly increased risk of developing T2DM compared to major allele homozygotes(TT genotype)(OR=2.240,95% CI=1.415-3.544,P=0.001). GG/GA genotype carriers of CAV1 rs3807986 had lower odds for T2DM than that of AA genotype(OR=0.640,95% CI=0.449-0.913,P=0.014). Compared with TT genotype,GG/GT genotype of CAV2 rs2270188 was a protective factor for T2DM(OR=0.616,95% CI=0.432-0.878,P=0.007). Significant genotype association with T2DM was also identified in CAV2 rs1052990(GG/GT versus TT genotype:OR=0.658,95% CI=0.453-0.956,P=0.028). Multiple linear regression showed that minor allele C of SNP rs926198 was associated with an increased level of HOMA-IR(beta=1.010,P<0.001) and minor allele G of SNP rs2270188 was associated with a decreased level of HOMA-IR(beta=-0.379,P=0.023). No significant association was identified between any SNP and HOMA-β.Allele G of CAV1 rs3807986 and CAV2 rs2270188 were also associated with a decreased level of LDL-C(P=0.033 and 0.030,respectively).[Conclusion]CAV1/CAV2 locus might be the candidate genes for conferring susceptibility to T2DM in the Chinese Han population.SNP rs926198, rs3807986,rs2270188,and rs1052990 in CAV1/CAV2 locus were associated with T2DM risk perhaps through insulin resistance pathway.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the renal protective effects of sulodexide and its anti-oxidative stress mechanism in diabetic rats.</p><p><b>METHOD</b>Thirty male SD rats were randomized into 3 equal groups, namely the control group, diabetic group, and sulodexide treatment group. Twelve weeks after establishment of rat diabetic models and administration of sulodexide, the rats were sacrificed for measurement of the urine volume, body mass, kidney mass/body weight ratio, plasma glucose, and glycosylated hemoglobin (HbA1c). Malondialdehyde (MDA) levels and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX) activities in the renal tissue or serum were tested. Electron microscopy was performed to observe the pathological changes in the kidneys.</p><p><b>RESULTS</b>The urine volume, renal mass/body mass ratio, serum glucose, HbA1C, and serum and renal MDA levels all significantly increased in the diabetic rats in comparison with the normal controls (P<0.05). But the body weight and activities of SOD, CAT, and GSH-PX in the renal tissue in the normal control group were significantly higher than those in the diabetic and sulodexide group. After 12 weeks of sulodexide treatment, SOD, CAT, and GSH-PX activities in the renal tissue of rats were significantly increased in comparison with those in the diabetic rats (P<0.05). Electron microscopy showed obvious irregular thickening of the glomerular capillary basement membrane in the diabetic group with vacuolization in the mitochondria in the epithelial cells, and such pathological changes were significantly alleviated in the sulodexide treatment group.</p><p><b>CONCLUSIONS</b>Sulodexide can effectively lower the urinary albumin excretion rate, improve the ultrastructural renal pathologies and prevent glomerular basement membrane thickening in diabetic rats, probably in association with the reduction of the MDA levels and enhancement of SOD, CAT, and GSH-PX activities.</p>