| Objectives:Type2diabetes mellitus (T2DM) is a metabolic disorder that is characterized by high blood sugar in the context of insulin resistance and relative lack of insulin. But the real pathogenesis and mechanism of T2DM is not known now. T2DM is rising all over the World.In2000, the number of T2DM was171million, however, there will be366million in2030. This increase will strain health systems already facing a high burden of t T2DM and its complication, such as renal failure,lose sight,diabetic foot and angiocarpy disease.From the estimation of WHO, the burden of T2DM will increase rapidly in world if we haven’t effective measure. For example, the burden of T2DM is24,500million in America in2012. And this burdent was higher41%than2007. T2DM combined with cancer and cardiovascular disease had been the three serious diseases in the world.In these thirty years, the prevenlence of T2DM is increase rapily in China too. The prevenlence of T2DM was0.67%in1980and2.5%in1994. However, the rate was up to9.7%in2007-2008. China has been the most number of T2DM in World. During the high disease burdent of T2DM, it needed to play some mesures on T2DM control and prevention in China too. Guangzhou is located in the south of China. The prevance of T2DM is higher than other middle and west city. Because the economic in Guangzhou is higher and abundant of diatery ways and other environment risk factors, risk factors of T2DM in Guangzhou are needed further research.T2DM is a complicated disease and relate to both genetic and environmental factors interact to produce hyperglycemia.There were over50genes had been found associated with T2DM, but the population attribute risk is very small in former research, new risk genes of T2DM also worth further research.There are no data regarding the possible role of the single nucleotide polymorphism (SNP) of class I Histone deacetylases (HDACs) in T2DM. Although SIRT1gene has been reported that it can increase the risk of Puma Indian.However, we haven’t found data in Chinese Han population. Furthermore, HDAC gene and SIRT1gene are deacetylases, the interaction of the two genes and T2DM worth further research.For environment risk factors, epidemiology data show that heavy weight or obesity is the risk factor of T2DM. Phicical activity including walking, exercise, etal will decrease the risk of T2DM.The relation of dringing and T2DM is U shape, little or heavy dringing had little risk of T2DM than normal dringing.Active or passive smoking will increase the risk of T2DM.Furthermore, unhealthy diatery mode will increase T2DM, however little fat and high carbohydrate will decrease T2DM. From the above, we know that T2DM is a complicated disease in which both genetic and environmental factors interact to produce hyperglycemia. We designed this study to examine whether polymorphisms of HDAC gene. SIRT1gene and other factors can be implicated in this disease.Methods:A community-based, case-control study was conducted, with a total of568subjects (284patients and284controls) enrolled. Eight polymorphisms of HDAC1(rs1741981), HDAC3(rs11741808, rs2547547, rs2530223) and SIRT1(rs4746720, rs10509291, rs2236319, rs10823116) were examined by the use of TaqMan technology. Dietary data were collected by an inquiring officer through a face-to-face method. Subjects’ body weights, heights and blood pressure were measured and recorded by a nurse. The levels of fasting serum glucose, triglyceride and total cholesterol was measured by a specialist using a Beckman Coulter AU680. We investigated the gene locus on the linkage disequilibrium and haplotype block analysis of the HapMap project data. SPSS13.0and Stata12.0were used to do the statistic.In demographic characteristics, the differences between the cases and controls were tested using the t test for continuous variables or χ2test for categorical variables; Multivariate logistic regression models were used to assess the effects of other factors and genotype on T2DM, controlling for the demographic characteristics such as gender, age, BMI, blood pressure, family income et al. The interaction between clinical factors and genotypes on T2DM were evaluated by multiplicative models.Results:There were no significant differences in the age or sex distribution between the control and the case (P values are0.109and1.000, respectively). Marital status, education and economic status had no significant differences too (P values are0.513,0.226and0.505).Compared with control, the case subjects showed higher levels of triglyceride and cholesterol, as well as BMI value (P<0.001, P=0.001and P=0.003, respectively).Behavior risk factors and T2DMThere were73(25.80%)smokers in type2diabetes mellitus group,72(25.44%) smokers in control group, no significant differences between the two groups (χ2=0.009, P=0.923). Moreover, there were50.35%population in type2diabetes mellitus group doing exercise over0.5h per day, however, in control group only27.56%population doing exercise over0.5h per day, the differences had statistical significant (x2=39.685, P<0.001).Compare with control, exam at regular interval, chronic disease history population have higher risk of type2diabetes mellitus.(χ2=19.796, P<0.001; x2=6.355, P=0.012, respectively).Diatary factors and T2DM11.27%case group population like to eat sour food,19.72%control group population like to eat sour food, there are significant differences between the two groups (x2=7.745, P=0.005). Otherwise, eating piquancy food, dringing milk, eat vegetable, plant oil and eat white meat will decrease the risk of T2DM (x2=4.397, P=0.036;x2=9.111, P=0.003;x2=30.968,P<0.001;χ2=25.227,P<0.001,χ2=12.756, P<0.001, respectively)We found significant association with risk of T2DM for three SNPs of HDAC3, including rs11741808[odds ratio (OR)=0.54,95%confidence interval (CI)=0.36-0.81], rs2547547[OR=1.72,95%CI=1.13-2.64], and rs2530223[OR=1.96;95%CI=1.04-3.68]. We found significant association with risk of T2DM for rs4746720CC+TT genotype compared with CT genotype [OR=1.42,95%CI=1.02-1.98].Subgroup analysis showed that BMI>23kg/m2, high triglyceride and high blood pressure, together with the rs11741808AG genotype, were associated with a significantly decreased risk for T2DM, with an OR of0.50(95%CI=0.27-0.91),0.38(95%CI=0.20-0.71) and0.43(95%CI=0.24-0.76) compared with AA genotype, respectively. In population with normal total cholesterol, the AG genotype was associated with a significantly decreased risk of T2DM risk, with an OR of0.42(95%CI=0.25-0.70) when compared with the persons of the AA genotype. For rs2547547, in population with normal total cholesterol and triglyceride, the AG genotype was associated with a significantly increased risk of T2DM, with an OR of1,92(95%CI=1.17-3.15) and2.24(95%CI=1.28-3.94) when compared with population carrying AA genotype. Further, we performed stratification analyses for SIRT1to explore the role of the polymorphism in the subgroup population. For rs4746720, subjects with high triglyceride harboring the CC or TT genotype had a significantly increased risk of type2DM [OR=1.85,(95%CI=1.06-3.23)] compared with subjects of the CT genotype. In subjects eat red meat more, the CC or TT genotype significantly increased type2DM risk[OR=1.43,(95%CI=1.01-2.02)] compared with subjects of the CT genotype. In analysis of the effect of sugary food or smoking, individuals with the CC or TT genotype of rs4746720had a significantly increased risk of type2DM compared with individuals carrying the CT genotype[OR=2.22,(95%CI=1.21-4.06)], and [OR=1.65,(95%CI=1.10-2.47)]. Multiple factors tests showed that high blood pressure, high triglyceride, high total cholesterol, BMI≥23and rs2547547AG compared with rs2547547AA+GG had higher risk of T2DM, with OR of2.23(95%CI=1.53-3.27),2.92(95%CI=1.98-4.31),1.50(95%CI=0.97-2.32),2.89(95%CI=1.98-4.21),1.93(95%CI=1.14-3.27), respectively. However, compared with rs2530223CT+CC, rs2530223TT+CC and rs11741808AA+GG, rs2530223TT, rs2530223CT and rs11741808AG had lower risk of type2DM, with OR of0.42(95%CI=0.20-0.87),0.33(95%CI=0.16-0.69),0.51(95%CI=0.32-0.81), respectively. Milk, soy, white meat, vegetables and low-salt diet decrease risk of T2DM, with OR of0.51(95%CI=0.29-0.88),0.43(95%CI=0.26-0.74),0.51(95%CI=0.32-0.83),0.21(95%CI=0.10-0.44),0.28(95%CI=0.12-0.65),0.35(95%CI=0.21-0.51) respectively. Red meat, salty food, BMI≥23kg/m2, use of animal fat and rs4746720CC+TT compared with rs4746720CT yielded higher risks of T2DM, with OR of2.89(95%CI=1.38-6.01),2.73(95%CI=1.61-4.64),3.47(95%CI=2.28-5.28),27.91(95%CI=9.24-84.32) and1.61(95%CI=1.06-2.44) respectively.We found no significant association between rs11741808and high triglyceride, BMI or high total cholesterol, the OR were1.35(95%CI=0.90-2.01),1.00(95%CI=0.67-1.50),0.96(95%CI=0.61-1.51), respectively. Moreover, there were no association between rs2547547, rs2530223and clinical character like BMI, high triglyceride, high total cholesterol too. And there were no association between SIRT1and clinical character like BMI, high triglyceride, high total cholesterol too.Conclusion:(1)The variance of HDAC (rs2530223, rs11741808and rs2547547) contribute to an increased prevalence of T2DM.(2)The variance of HDAC (rs1741981) has no relation with T2DM.(3) The variance of SIRT1(rs4746720) contribute to an increased prevalence of T2DM.(4) The variance of SIRT1(rs10509291, rs2236319and rs10823116) has no relation with T2DM.(5)Dringing milk, eat vegetable, eat sour food, et al were protect factors of T2DM.(6)Eating red meat, salt food and eating animal oil were risk factors of T2DM.(7)High blood pressure, high triglyceride, high total cholesterol an BMI≥23kg/m2were risk factors of T2DM.(8)No interaction relations were found between gene, environmental factors and T2DM. |
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