| objective: Diabetes mellitus(DM) has become the third major non-infectious diseases to harm human health after the cardiovascular disease and malignant tumors. Recent decades, the incidence of DM sharply increased and it seriously affected the patient’s life and healthy in our country. The pathogenesis of diabetes have not been completely clarified.At present, it is generally recognized that DM is a chronic inflammatory disease, and it is one of the important causes of islet beta cell dysfunction because of long-term high blood glucose, high free fatty acid(FFA), superabundant islet amyloid polypeptide(IAPP) deposition and interleukin-1β(IL-1β) and other chronic inflammatory factor stimulation. it is found that apoptosis is the main change of islet beta cell dysfunction in the patients with type 2 diabetes mellitus(T2DM). In order to predict the risk of developing T2 DM,the study takes the Han population in Lu zhou area as the research object to explore the relationship between CASP8-652 6N I/D polymorphism and prediabetes and T2 DM.Methods:(1) All of experimental objects come from the Han population without genetic relationship in Lu zhou area of Si Chuan Province. The participator derived from the samples of the epidemiological investigation, and were divided into prediabetic group(478 cases) with normal triglyceride(TG)(348 cases) or high TG(130 cases); T2 DM group(444 cases) with normal TG(312 cases) or high TG(132 cases); the control group comes from the healthy population ofepidemiological survey(352 cases).(2) genomic DNA samples were extracted, then targeted DNA fragments were amplified by PCR and identified genotyping using restriction fragment length polymorphism(RFLP) analysis, finally DNA sequencing method was used to verify the accuracy of genotyping.(3) Statistical analysis: Hardy-Weinberg equilibrium was used to analyze representativeness of the selected samples. Clinical variables and biochemical indexes were represented by mean ± standard deviation( x ±s). average values between groups uses t test. Chi-squared test was used to analyze the variables of genotype frequency and allele frequency between the groups. And P<0.05 was considered statistically significance. Statistical analysis were processed using SPSS software(Version 22.0; SPSS Inc., Chicago, USA).Results:(1) The samples of control group, prediabetic group and T2 DM group were accord with the Hardy-Weinberg equilibrium(P>0.05) indicating that the gene distribution of selected samples accorded with the genetic equilibrium.(2) the gene frequency were 56.5%(I/I), 39.2%(I/D), 4.3%(D/D) in control group;63.8%(I/I), 29.6%(I/D), 6.6%(D/D) in prediabetic group with normal TG;53.8%(I/I), 40.8%(I/D), 5.4%(D/D) in prediabetes with high TG; 57.7%(I/I), 33.6%(I/D), 8.7%(D/D) in T2 DM group with normal TG; 50.8%(I/I), 45.4%(I/D), 3.8%(D/D) in T2 DM with high TG groups. The difference of gene frequency in the prediabetes with high TG group and T2 DM with high TG group compared with the control group were no statistical significance(P > 0.05), and gene frequency in the prediabetes with normal TG group and T2 DM group withnormal TG group compared with the control group has statistically significant difference(P < 0.05).(3) Compared with the I/I genotype, the incidence of prediabetes with normal TG(P values < 0.05 and adjusted OR was 0.669) decreased in I/D gene type; the frequency of allele I and D in control group and prediabetes(normal TG) group were 76.1%, 23.9% and 78.6%,21.4% respectively; compared with the I/I+I/D genotype, the incidence of T2DM(normal TG)(P values < 0.05 and adjusted OR was 2.128) increased in D/D gene type; the frequency of allele I and D in the control group and T2DM(normal TG) group were 76.1%, 23.9% and 74.5%,24.5% respectively; the difference was no statistically significant. The I/D and I/I genotype in T2DM(normal TG) group merged into a group, then compared with D/D genetype in T2DM(normal TG) group found that fasting blood glucose of D/D genotype was higher than that of I/D and I/I genotypes, the difference was statistically significant(P<0.05); the blood glucose of D/D genotype compared with I/D and the I/I genotype in the prediabetes(normal TG) group were no significant difference. Body mass index(BMI),postprandial 2 hours blood glucose levels and glycosylated hemoglobin levels were were no statistical significant difference.(4) The fasting blood glucose, postprandial 2 hour blood glucose, cholesterol and low density lipoprotein in prediabetes with high TG group were higher than that in prediabetic with normal TG group(P<0.05), The high density lipoprotein, gender,BMI, glycosylated hemoglobin, age of onset between two groups were no statistical significant difference.(5) Thecholesteroland and low density lipoprotein in the T2 DM with high TG group were higher than that in the T2 DM with normal TG group(P<0.05). The BMI, age of onset, gender,fasting blood glucose, postprandial 2 hour blood glucose, high density lipoprotein and glycosylated hemoglobin between two groups showed no statistical significance.(6) The cholesterol, TG, low density lipoprotein and age of onset in the T2 DM with high TG group were higher than that in the prediabetes with high TG group(P<0.05), The high density lipoprotein and gender between two groups showed no statistical significance. Conclusion:(1) CASP8-652 6N I/D polymorphism was related to incidence of prediabetes and T2 DM with normal TG in Lu Zhou area of Han People. Compared with the I/I genotype, the incidence of prediabetes with normal TG decreased in I/D gene type. Compared with the I/D+I/I genotype, the incidence of T2 DM with normal TG increased in D/D gene type;(2) CASP8-652 6N I/D polymorphism was not related to incidence of prediabetes with high TG and T2 DM with high TG in Lu Zhou area of Han People.(3) The fasting glucose, postprandial 2 hour blood glucose, cholesterol level and low density lipoprotein in prediabetes with high TG group were higher compared with that in prediabetes group.(4) The cholesterol level and low density lipoprotein in T2 DM with high TG group was higher than that in T2 DM group with normal TG.(5) T2 DM with high TG group were higher than prediabetes with high TG group in TG, cholesterol levels, low density lipoprotein and age of onset. |
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