The Study Of The Risk Factors For Dyslipidemia And The Relevance Between Dyslipidemia And Genes Associated With Lipid Metabolism

Background and objectiveDyslipidemia refers to the abnormalities of serum lipid metabolism, including higher levels of total cholesterol (TC), triglycerides (TG), and low density lipoprotein cholesterol (LDL-C) , and lower level of high-density lipoprotein cholesterol (HDL-C) . Many researches have showed that dyslipidemia is an important risk factor of various diseases such as hypertension, type 2 diabetes, stroke, atherosclerosis and coronary heart disease. With the development of economy in China, the improvement of people’s living standard, and the chang of living and eating habits, the incidence of chronic diseases such as dyslipidemia has increased significantly. Lipid levels have closely relation with living and eating habits. Chaoshan located in coastal and the local residents have a unique traditional custom culture, living and eating habits for a long time. Our initial survey has found that the rate of dyslipidemia in this population was more than 40 percent, and dyslipidemia includs high cholesterol and high triglycerides primarily. Dyslipidemia has become one of the important chronic non-communicable diseases which have harmful affects on the health of chaoshan people, however, at present the environmental risk factors of dyslipidemia in the population has not been system reported.Besides the environment factors, dyslipidemia was also affected by genetic factors. Many studies have showed that apolipoprotein E and lipoprotein of lipase were important factors in the regulation of lipid metabolism, the genetic polymorphism of which was the significant genetic factors that effect of plasma lipoproteins. Genome-Wide Association Studies (GWAS) has confirmed that ApoErs157580 and LPL rs326 associated with hyperlipidemia were the dangerouse label SNP sites in European population. However, the relationship between the SNP sites and dyslipidemia has not yet been confirmed in all of the people especially in eastern Asia. In this study, we researched the enviromental factors in chaoshan population by case-control method to find the risk factors of dyslipidemia. Meanwhile, we also detected rs157580 and rs326 gene polymorphism and analyzed the association between them and dyslipidemia. We further explore the relations of interaction of gene-gene and gene-environment to dyslipidemia. The aim of our study was to carry out the effective intervening measures to promote health and reduce the risk of cardiovascular diseas.Materials and methodsFrom May 2010 to December 2010, we selected subjects from Physical Examination Center of ChaoNan minsheng hospitals and the first affiliated hospital of medical college of Shantou university by cluster sampling method. All the subjects, more than 18 ages, have been in chaoshan for more than 5 years. We used epidemiologic survey method to collect datas including body measurement, questionnaire and biochemical examination. In order to research the relation of environmental risk factors to dyslipidemia by case-control method, we selected 1120 patients with dyslipidemia, including 923 male and 197 female, average ages 44.1±11.6 years, and 1021 cases with not dyslipidemia, including 694 male and 327 femal, average ages 38.7±1.7 years.In order to further explore the relationship between dyslipidemia and gene polymorphism related with lipid metabolism, we paired the objects according to age and gender and selected 384 pair’s cases and controls randomly. We detected ApoE rs157580 and LPL rs326 SNP sites by Beckman SNPstream technology to analyze the relationship between dyslipidemia and these two gene polymorphisms.We established database and logged data by EpiData3.0. After checked the data, we use SAS9.1 and SPSS13.0 software to analyze them. We checked the normality of measure data by single sample K-S goodness-of-fit method. For the data which was non-normal distribution, we transformed it to normal distribution by logarithmic method. For the grouped case-control study, we used t-test to compare the quantitative variables of two groups and ANOVA test to compare measurement variance of more than two groups. We use ratio to descripe the enumeration data andχ2 test to do statistic inference. To research the relationship between environmental factors and dyslipidemia, we used the single factor and multifactors unconditional logistic regression. For the paired case-control study, we used pairedχ2 test to analyze the enumeration data, and conditions logistic regression to analyze the relationship between environment factors and dyslipidemia. We used Haploview software to analyze the Hardy-Weinberg balanced test and gene polymorphism, and GMDR software to analyze the interaction of gene and gene and of genes and environment. Significant test level was alpha=0.05.Results1. Physical examination indexes and biochemical indexes were higher in dyslipidemia crowd than normal population (P < 0.05).2. Multivariate Logistic regression showed that risk factors of dyslipidemia in the chaoshan people were age (OR = 1.04), sitting time (OR = 1.24), drinking (OR = 1.16), inkfish intake (OR = 1.14) and pickle intake (OR = 1.10), body mass index (OR = 196), blood glucose abnormalities (OR = 1.91); Protection factor were female (OR = 0.58), exercise frequency (OR = 0.79).3. The distribution of ApoE rs157580 C>T and LPL rs326 T>C accorded with Hardy-Weinberg balance. The difference of allele and genotype frequency of rs157580 C > T between cases and controls was not statistically significant (P = 0.918, P = 0.743 respectively). The allele frequency of rs326 T>C was not different between cases and controls (P = 0.067), but the difference of genotype frequency between cases and controls was statistically significant (P = 0.012). Adjusted by dyslipidemia risk factors, the group which contains allele T (CT + TT) of rs326 C>T has a higher risk for dyslipidemia than CC genetic type carrier (P < 0.05).4. Adjusted by dyslipidemia risk factors, there was interaction between rs157580 C>T and the rs326 C>T. TT genetype of rs157580 C>T and CT, TT genetype of rs326 T>C increase risk for dyslipidemia together, aOR = 3.5 (95% CI: 1.1-11.2, P = 0.035).5 Adjusted by risk factors, there was interaction between rs157580 C>T and BMI and also between rs326 T>C and BMI. TT genetype of rs157580 C>T and CT, TT genetype of rs326 T > C exist synergistic effect with BMI for dyslipidemia.Conclusions1. Age, sitting time, drinking, inkfish intake, pickled food intake, BMI, blood glucose abnormalities were the risk factors for dyslipidemia; women and exercise frequency were protect factors for dyslipidemia.2. LPL rs326 T>C is one risk factor of dyslipidemia.3. TT genetype of rs157580 C>T and CT, TT genetype of rs326 T>C increase risk for dyslipidemia together.4. TT genetype of rs157580 C>T and CT, TT genetype of rs326 T>C exist synergistic effect with BMI for dyslipidemia.