Association Between Polymorphism Of ANGPTL8 Gene And Carotid Artery Intima-media Thickness In Type 2 Diabetes Mellitus

ObjectiveTo investigate the relationship between the rs2278426 polymorphism of ANGPTL8 gene and carotid artery intima-media thickness in patients with type 2 diabetes mellitus(T2DM)MethodsIn this study,418 subjects were included,217 of them were T2DM patients(T2DM group),and 201 were normal glucose tolerance(NGT group).According to the carotid intima-media thickness(cIMT),T2DM patients were divided into two groups T2DM patients without carotid intima thickening(109 cases)and T2DM patients with carotid intima thickening(108 cases).The basic parameters of human body and biochemical indexes of all the subjects were measured by the unified measurement method and standard.The whole genome DNA of the subjects was extracted and the polymorphism of rs2278426 in angptl8 gene was detected by PCR and RELP.The accuracy of PCR-RELP genotyping was verified by two-way gene sequencing.Chi square test(χ2test)was used to compare the frequency differences of rs2278426 genotype and allele between the two groups,and Student-t or Mann Whitney U test was used to compare the differences of biochemical indexes between the two groupsResults(1)Compared with NGT group,Body mass index(BMI),neck circumference(NC),waist circumference(WC),hip circumference(HC),waist to hip ratio(WHR),systolic blood pressure(SBP),triglyceride(TG),fasting blood glucose(FPG),fasting insulin(FIns),2-hour blood glucose(2hPG)in OGTT test,2-hour insulin(2hIns)in OGTT test,insulin resistance index(HOMA-IR)and HbAlc in T2DM group The difference was statistically significant(P<0.05)(2)Compared with T2DM without carotid intima thickening,the age,HC,SBP,DBP,TG and FIns and of T2DM with carotid intima thickening were significantly higher(P<0.05)(3)In NGT group,CC genotype was 65.2%,CT genotype was 29.9%,TT genotype was 5.0%;in T2DM group,CC genotype was 54.4%,CT genotype was 38.7%,TT genotype was 6.9%.The genotype distribution between NGT group and T2DM group was statistically different,and the frequency of CT genotype in T2DM group increased significantly(P<0.05).The frequency of CT+TT genotype in T2DM group increased significantly(P<0.05).The distribution of rs2278426 alleles between the two groups was statistically different(P<0.05),and T allele frequency was significantly higher in T2DM group(4)In T2DM group,the genotype distribution of T2DM without carotid intimal thickening group was:CC genotype 65.1%,CT genotype 29.4%,TT genotype 5.5%;in T2DM group,CC genotype 43.5%,CT genotype 48.1%,TT genotype 8.3%.There was significant difference in genotype distribution between the two groups(P<0.05).The frequency of CT genotype was significantly higher in T2DM carotid intimal thickening group,while the frequency of CC genotype was significantly lower(P<0.05).In the dominant model,compared with T2DM group(34.9%),the frequency of CT+TT genotype in T2DM group(56.5%)increased significantly(P<0.05).The frequency of T allele in T2DM group was significantly higher than that in T2DM group(P<0.05)(5)In the total population,WHR,TG,2hPG,FIns and HOMA-IR of CT+TT genotype were significantly higher than those of CC genotype(P<0.05).In NGT group,TG level of CT+TT genotype carriers increased significantly(P<0.05).In T2DM group,The TG of CT+TT genotype were significantly higher than those of CC genotype,while HDL-C was significantly lower than those of CC genotype(P<0.05)(6)The results of multivariate logistic regression analysis showed that the rs2278426 T allele of ANGPTL8 gene was an independent risk factor for carotid intimal thickening in T2DM(P=0.003,OR=2.557,95%CI=(1.381-4.734))ConclusionThe genotype distribution of ANGPTL8 rs2278426 is related to carotid artery intima-media thickness in T2DM.Compared with T2DM without carotid intima thickening,T2DM with carotid intima thickening had higher frequency of CT+TT genotype and T allele,which indicated that carrying T allele might increase the risk of carotid intima thickening in type 2 diabetes.