A Case-control Study On The Clinical Features Of LADA And The Association Between CTLA-4 Gene Polymorphism And LADA

Objective:To compare and analyze the clinical features of latent autoimmune diabetes in adults(LADA)and type 2 diabetes mellitus(T2DM).To explore the risk factors of LADA,especially the association between the polymorphism of cytotoxic T lymphocyte-associated antigen 4(CTLA-4)gene and LADA.To provid scientific evidence for illuminating the causes of LADA,screening the susceptible population and making effective preventive measure and control measure.Methods:From data of the cross-sectional study of diabetes in Tianjin from June to July in 2005,the clinical features of 46 patients with LADA and 452 patients with T2DM were compared.1:4 matched case-control study was carried out for exploring risk factors of LADA.PCR-RFLP was used to detect the CTLA-4 polymorphism. Conditional Logistic regression was used to analyze the associations between CTLA-4 polymorphism,other factors and LADA.Results:1.The results of comparing general state and clinical features in LADA and T2DM groups showed that proportion of persons under 60 years old group(78.3%)in LADA patients was higher than 60.4%in T2DM patients(χ~2=5.657,P=0.017),the proportion of only using insulin injection in LADA patients(15.4%)is higher than 0.9%in T2DM patients(χ~2=15.471,P＜0.001),the average systolic blood pressure in LADA patients(127.57±18.50mmHg)was lower than 133.71±18.81 mmHg in T2DM patients(t=2.070,P=0.039),and the average of very low density lipoprotein cholesterol(VLDL-C)level in LADA patients(0.53±0.27mmol/L)was lower than 0.66±0.35mmol/L in T2DM patients(t=2.358,P=0.019).There were no statistical significant differences in average age diagnosed as diabetes,course of diabetes, fasting blood glucose.postprandial blood sugar,diabetic complications,the condition of glucose control,ketosis,family histories of diabetes and hypertension,average diastolic blood pressure,average TC,TG,HDL-C and LDL-C levels between the two groups.2.The frequencies of genetype CC and genetype CT in CTLA-4 promotor -318 site were 62.5%and 37.5%in LADA group,81.8%and 18.2%in T2DM group,82.0% and 18.0%in nondiabetes group respectively(χ~2= 9.917,P=0.007).The distribution of allele C and allele T frequencies were significantly different in three groups.The frequencies of genetype AA,AG and GG in CTLA-4 exonl 49 site were 8.3%,60.4% and 41.3%in LADA group,30.7%,53.1%and 16.1%in T2DM group,64.6%,27.1% and 8.3%in nondiabetes group(χ~2=75.010,P＜0.001).The frequencies of allele A and allele G in LADA group were higher than the frequencies in T2DM group and nondiabetes group.3.Comparing with nondiabetes controls,the results of univariate cox regression analysis showed that the family history of diabetes,CTLA-4 promotor and exonl gene mutation,intellectual work,meat intake,irregular three meals were the risk factors of LADA,the OR and 95%CI were 2.358(1.168-4.760),3.711(1.834-7.511),4.705(2.671-8.290),2.872(1.121-7.355),1.531(1.050-2.233)and 2.778(1.344-5.743) respectively.No associations between the nation,culture level,marital condition, income,smoking,drinking,physical exercise,the intakes of main food,fish,poultry, milk,egg,vegetable and fruit,the intake of sweet food,inregular breakfast,BMI, WHR,systolic blood pressure,diastolic blood pressure,character,hypertension, psychic trauma,the history of hyperlipoidemia,the family histories of hypertension and heart disease and LADA were found.The results of multivariate cox regression analysis showed that inregular three meals,polymorphisms of CTLA-4 promoter C/T and exonl A/G,the history of diabetes were the risk factors of LADA,and the OR and 95%CI are 4.920(1.750-13.834),4.205(1.677-10.545),7.330(3.430-15.665) and 3.497(1.327-9.214).4.Comparing with type 2 diabetes controls,the results of cox regression analysis showed that polymorphisms of CTLA-4 promoter C/T and exonl A/G were associated with high risk of LADA.Conclusion:The proportion of persons under 60 years old group and only using insulin injection in LADA patients were higher than in T2DM patients.Clinically,the average systolic blood pressure and VLDA-C level in LADA patients were lower than in T2DM patients.The genetype frequencies in -318 site of CTLA-4 promotor and 49 site of CTLA-4 exon 1 were significantly different in LADA,T2DM and nondiabetes groups.The irregular three meals,the gene mutation of CTLA-4 exonl and promoter and family history of diabetes were the risk factors of LADA.