Association Analysis Between Liability Of Complicating Nonalcoholic Fatty Liver Disease Of Type 2 Diabetes Patient With Adipokines SNPs.

Nonalcoholic fatty liver disease is a clinical-patho-syndrome related with environment-heredity-metabolism stress. It always exists accompanied with Type 2 Diabetes. Recently, with the increase of morbidity rate of obesity and Type 2 Diabetes, Type 2 Diabetes complicating nonalcoholic fatty liver disease also increases obviously. Morbidity is higher than that of common crowd. Morbidity of Type 2 Diabetes patients who are fat can reach 100%. The existence of diabetic aggravates liver damage and hastens fatty liver into liver fibrosis and liver cancer. Also the emerge of fatty liver raises the mortality of Type 2 Diabetes patient. So it is significant to screen the liability factors of Type 2 Diabetes patients who complicated nonalcoholic fatty liver disease. Case-control study was applied in this study. The life style complication, medication and biochemical indicator of Type 2 Diabetes patients were taken as environmental factors. Parts of genetic locus of adipokines such as Leptin, adiponectin, resistin, TNF-α, Visfatin were taken as genetic factors. The association of the liability of complicating nonalcoholic fatty liver disease of Type 2 Diabetes patient with the interaction between genetic factor and environmental factors was investigated to obtain more significant liability factors to pave a road for early diagnosis, prevention and cure for this disease.This study took 208 Type 2 Diabetes patients who came from yunyang region in Hupeh province Han population as case group, it comprised 98 patients with nonalcoholic fatty liver disease and 110 patients without it. 100 people who were healthy were chosed as normal control. These two groups could match in sex and age. All subjects hadn′t blood relationship. All had signed informed consent.Firstly, the data of environmental factor such as living condition, complication, application of antidiabetic drug and clinical index was obtained by questionnaire; SNPs of some adipokines gene were detected by LDR sequencing and typing method, they were LEP-2548G>A, RETN-420C>G, PBEF-3186C>T, PBEF-2423A>G, PBEF-1001T>G, TNF-α-238A>G and APM1+45T>G. Lastly, association analysis was carried out through statistical means. chi-square test was used to compare the difference of numeration data between groups. t-test was used to compare the difference of measurement data between groups. OR and 95%CI were used to estimate association intensity between each risk factor and disease. Last completing the screen of liability factors through multiple factor Logistic regression analysis.The following are the major results obtained in this study.1. Of all the 37 environmental factor, the metabolism syndrome, complicating biliary tree stone, applying oral antidiabetic drug, WHR, BMI, DBP,ALT, AST,γ-GT,TG, AU,LP, FPG, FC-P, intensity of physical work and apply of insulin were different between Type 2 Diabetes patients who complicating nonalcoholic fatty liver disease and who were not (P<0.05).2. Multiple factor Logistic regression analysis:BMI, FC-P, AU, ALT, TG, FPG and complicating biliary tree stone were Risk factors(OR<1), apply of insulin was protection factor(OR<1).3. SNP detection rate of the 7 locus were above 98.05%, PBEF-2423A>G was not seen in all subjects, the aberration rate of PBEF-1001T>G was low(2.32%), mainly in normal control. The distribution of 3 SNPs of PBEF was different with un-Asian population(P<0.001).4. the genotypic distributions of all 5 SNPs(except for PBEF-2423A>G, PBEF-1001T>G) of all subjects were not deviated from the H-W equilibrium (P>0.05).5.Between normal control, group including patients complicating nonalcoholic fatty liver disease and group including Type 2 Diabetes patients not complicating nonalcoholic fatty liver disease, distribution of SNP of LEP-2548G>A had significant difference(P<0.01), AA genotype had higher risk of complicating nonalcoholic fatty liver disease(P<0.05). it was 3.080 times bigger than that of AG (OR=3.080,CI 1.515～6.246)and it was 2.287 times bigger than that of G allele carrier (OR=2.287,CI 1.185～4.416). The distribution of SNPs of PBEF-3186 C>T,TNF-α-238A>G, APM1+45T>G and RETN-420C>G hadn't significant difference among the three groups(P>0.05).6. SNP distribution of leptin gene -2548G>A hadn′t significant difference between different sex and different BMI (P>0.05), but distribution was correlated with mid abdomen fatty, Among the total, LEP-2548AA genetype had higher risk of mid abdomen fatty, was 2.720 times bigger than GG(OR=2.720,CI 1.186～6.235,P<0.05). The distribution of other 4 SNPs hadn′t significant difference between fatty and not, and between different sex (P>0.05).7. Type 2 Diabetes patients with different genotype of LEP-2548G>A hadn′t significant difference in ALT,AST,γ-GT,TG, AU,LP,FPG, FC-P and in the degree of fatty liver (P>0.05).8. LEP-2548G>A genetype as a independent variable was associated with liability of complicating nonalcoholic fatty liver disease of Type 2 Diabetes patient. AA genotype was the Risk factor of nonalcoholic fatty liver disease of Type 2 Diabetes patient (OR=3.035,CI 1.210～7.615,P<0.05). -2548AA genotype may increase the risk of mid abdomen fatty and hasten Type 2 Diabetes patient to develop complicating nonalcoholic fatty liver disease through regulating distribution of fatty. So maybe LEP-2548G>A locus was the susceptibility gene locus.The findings above will contribute to perfect the pathogenesy of Type 2 Diabetes patient complicating nonalcoholic fatty liver disease and settle grave experimental foundation for predicting individual onset risk and set up diagnostic method and judge prognosis and guide therapy.