Fetuin-A Polymorphism, Atherosclerosis Correlation Between Plasma Levels And Type 2 Diabetes And Lower Limb Arteries

[Objective] The aim of this study was to investigate the allele and genotype frequency distribution of four single nucleotide polymorphism (SNP) sites (rs1071592, rs2248690, rs4917and rs4918) in the Fetuin-A gene. Specifically, we wanted to evaluate these SNPs for the association of gene polymorphisms and altered serum Fetuin-A concentrations with type2diabetes (T2DM) in the minority Yi population of Chuxiong.[Methods] Four SNPs in Fetuin-A were genotyped in128T2DM cases and120normal controls by polymerase chain reaction-restricted fragment length polymorphism(PCR-RFLP) and allelic specific primer-PCR (ASP-PCR). The plasma levels of Fetuin-A were detected by enzyme linked immuno sorbent assay (EL1SA). Genotype frequencies, allele frequencies and clinical indexes were compared among groups.[Results]①The CC genotype and allele C of rs1071592were higher in type2diabetes than in normal controls (X2=7.215, p=0.007; X2=10.789, p=0.001);②there were no significant differences in frequency of genotype and allele distributions in the polymorphism analysis of rs4917, rs4918and rs2248690in these two groups (P>0.05);③The plasma Fetuin-A levels were higher in T2DM group (348.88±48.18ug/ml) than in NC group (283.09±40.72ug/ml) and the difference has statistical significance after covariance analysis (P<0.01).④There was a positive correlation between plasma Fetuin-A and insulin sensitivity index (ISI), total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL) and blood urea nitrogen (BUN)(r=0.175、0.284、0.296、0.312、P<0.05).A negative correlation with high density lipoprotein (HDL)(r=-0.153, P<0.05) was observed. Multiple stepwise regression analysis showed that ISI, HDL and BUN were independent determinants for plasma Fetuin-A concentrations (B=3.126,-12.092,7.073, P<0.05).⑤Logistic regression analysis showedthat plasma Fetuin-A level, systolic blood pressure (SBP), TG, LDL and fasting blood glucose (FBG) were independent determinants in T2DM patients (OR=1.070,1.127,16.858,82.333,56.657)[Conclusion]①The Fetuin-A gene rs1071592, rs2248690, rs4917and rs4918polymorphism was accurately analyzed by ASP-PCR,PCR-RFLP.②The rs1071592(A/C), rs2248690(A/T), rs4917(C/T) and rs4918(C/G) sites of Fetuin-A gene exist polymorphisms in the minority Yi of chuxiong.③The plasma Fetuin-A level was elevated in T2DM, and it was independently associated with insulin resistance index. Fetuin-A levels may be a reaction monitoring indicators of insulin resistance and type2diabetes. [Objective] Diabetic atherosclerosis of lower limb arteries (ALL A) is a devastating pathological condition which can ultimately lead to the nontraumatic amputation in type2diabetes mellitus (T2DM). The ability to identify the novel risk factors will allow us to eliminate ischemic symptoms and prevent progression to vascular occlusion. We therefore propose to determine the correlation between plasma Fetuin-A level and gene polymorphism with the development of ALLA in patients with T2DM. This study focused on T2DM patients belonging to the minority Yi population of Chuxiong in Yunnan Province.[Methods] A case-control study was applied. The lumen diameter and intima integrity of major lower limb arteries were examined by Aloka al0Doppler ultrasound. Subjects consist of120normal controls,61T2DM cases and67diabetic ALLA patients. The genotype frequencies, allele frequencies and clinical index were compared among groups.[Results](1) There was a significantly greater frequency of the C/C genotype and allele C of rs1071592in ALLA-T2DM versus normal controls (X2=9.254, p=0.002, X2=11.670, p=0.001).(2) There were no significant differences in genotype or allele distributions according to polymorphism analyses of rs4917(C/T), rs4918(C/G), and rs2248690(A/T)(p>0.05).(3) The plasma levels of Fetuin-A were elevated in the T2DM group (332.48±42.66ug/ml) versus healthy controls (283.09±40.72ug/ml), and were the greatest in ALLA-T2DM (363.80±48.35ug/ml). A statistically significant difference was revealed after performing covariance analysis on the data (p<0.01).(4) There was a positive correlation between plasma Fetuin-A, ALLA scores, and lower extremity arterial intima-media thickness (r=0.407,0.409,0.462, p<0.001), but no significant correlation with intimal calcification or phosphate deposition (r=0.041,-0.148, p>0.05).(5) Logistic regression analyses showed that plasma Fetuin-A levels and the C/C genotypes of rs1071592, TG, FBG, BMI, and SCR were independent determinants in ALLA-T2DM (OR=1.024,7.989,2.084,1.736,0.572,1.070).[Conclusions](1) The C/C genotype of rs1071592is associated with ALLA in the Yi type2diabetes patient population tested in this study.(2) There was a positive correlation between plasma Fetuin-A, ALLA scores, and lower extremity arterial intima-media thickness, but no significant correlation with intimal calcium or phosphate deposition.(3) The level of plasma Fetuin-A may be a reliable predictor of ALLA in type2diabetes. The results of our Fetuin-A research present an opportunity to develop a unique diagnostic/prognostic tool in the battle to against ALLA in type2diabetics. Additional studies on an expanded population will confirm the utility of Fetuin-A polymorphism testing for risk determination.