Study On The Relationship Between The Interaction Of Diet And Gene With The Abnormal Body Fluid Of Uygur Medical

Objective:In order to find out the distribution area of Kashi Uygur adults in different Uyghur Medicine Hilit,dietary structure and nutrition analysis of the population intake distribution, to explore the relationship between dietary patterns and the abnormal Hilit of Uygur medical, explores the relationship between gene polymorphism and Uyghur Medicine Hilit, explore the combined effect of gene-gene and gene-environment of Uighur Medicine abnormal Hilit risk, from the traditional Chinese Medicine, epidemiology, nutrition, environmental, genetics and other multiple angle of Uyghur Medicine Hilit essence to elaborate, in order to enrich the Uygur Medicine fluid on the connotation and denotation, providing basic theoretical for the diagnosis and treatment of the Uyghur Medicine fluid disease in the future. Methods:The research object of the natural population of the Uygur nationality in Kashi area of Xinjiang, taked the combination of field epidemiological investigation and laboratory testing, questionnaire investigation, diet investigation, physical examination, blood sample collection and detection were carried out one by one to meet the inclusion criteria, the dietary patterns of the population were constructed by factor analysis, and the ACE gene and ApoE gene polymorphism were detected by high resolution melting curve and polymerase chain reaction,used crossover analysis and multifactor dimensionality reduction analysis of gene-gene and gene-environment interaction with the high order Uighur Medicine abnormal Hilit risk. Results:1.the epidemiological investigation of the body fluid of Uygur adults（1） The survey of adults in Kashgar group in Uyghur Medicine abnormal Hilit overall prevalence rate was 73.85%, men overall prevalence rate was 71.54% and female overall prevalence rate of 75.42%, abnormal body fluid of male and female prevalence rate than 0.95: 1, male and female overall prevalence rate distribution was different. Abnormal Hilit population prevalence rate decreased with the increase of age and change trend has gender difference（χ²=24.922, P=0.000）, and the incidence rate in male has continued to rise with age increasing, the prevalence rate of female was presented the trend of first increased and then decreased. Four kinds of abnormal Hilit in male, with age, kan type and savda prevalence rate was the rising trend, while the sapra type and phlegmatic type is decreased; Female with the age increases, the kan type was increased continuously, while the biliary fluid and the black biliary type showed a trend of first rise and then decreased.（2） Males and females in different dimensional medical Hilit of BMI, WHR, WHtR, SBP, DBP, TG, HDL-C mean distribution difference was statistically significant（P<0.05）, FPG, TC, LDL-C mean distribution difference were not statistically significant（P>0.05）. According to the BMI groups of normal Hilit obese rate were 21.8%, according to WHR groups of male and female obesity rates were 21.5% and 26.6%; according to the grouping of BMI abnormal humoral medium obesity rate was 34.7%, according to WHR groups of male and female obesity rate was 27.5% and 42.5%, respectively. Normal Hilit in hypertension group and hyperglycemia prevalence rate was 6.4% and 5.1%, abnormal Hilit hypertension and hyperglycemia prevalence rate of 19.9% and 16.1%, abnormal Hilit hypertension and hyperglycemia prevalence rate were higher than those of normal Hilit group（χ²=29.523, P=0.000; χ²=23.272, P=0.000）.2.Study on the relationship between dietary patterns and the body fluid of the Uygur adults（1） The survey in Kashi area adult natural population has four major dietary patterns, namely grain vegetable dietary patterns, fruit milk type of dietary patterns, meat egg of dietary patterns and dried fruits and nuts type dietary pattern. There were differences in the dietary patterns of male and female, and the dietary patterns of urban and rural residents were different. In grain valley vegetable and fruit milk type of dietary pattern mainly to low into the above the age of 60 elderly people, mostly, in meat and egg type dietary patterns mainly to low 40 year old middle-aged person majority, in dried fruits and nuts dietary pattern mainly to score of 18 to 30 years old youth for habitat. Four types of dietary patterns in the normal bile liquid, blood and mucus in the composition of the main grain- based vegetables, and the black bile was the main type of meat eggs.（2） There were significant differences in the distribution of BMI, WHtR, SBP, DBP and FPG between male and female in different dietary patterns（P<0.05）. No correlation between the MS and the its components（P>0.05） of the dietary pattern of grain and vegetables. The fruit milk types of dietary patterns and MS and hypertension rate was negative correlation, the high consumption of individual suffering from MS and hypertension risk are low 0.41 times and 0.33 times（95% CI: 0.22⁰.87; 95% CI: 0.25⁰.92） and MS and hypertension incidence showed a linear decreasing trend(P_{MS trend}=0.027; P_{hypertension trend}=0.033) in the mode of low, medium and high quantile.（3） Meat egg type of dietary pattern and high fasting glucose and obesity is positively related to the high quantile intake of individual suffering from high fasting glucose and obesity are low 1.35 times and 3.26 times（95% CI: 0.89².84; 95% CI: 2.21⁵.71）, and high fasting glucose and obesity risk rate in the mode of low, medium and high quantile linearly increasing trend(P_{high fasting blood glucose trend}=0.006; P_{obesity trend}=0.000). Dried fruits and nuts dietary patterns and high fasting glucose showed negative correlation, the high quantile intake of individual suffering from high fasting blood glucose is low 0.20 times（95% CI: 0.12⁰.75） and high quantile fasting blood glucose, suffering from rate shows a linear decreasing trend(P_{high fasting blood glucose trends}=0.014) in the mode of low, medium and high quantile.3. Association of polymorphisms of ACE gene and ApoE gene with genetic susceptibility to abnormal body fluid in Uygur（1） ACE gene rs4353 genotype in the case group and controlgroup were mainly AG genotype, AG genotype distribution in the case group and the controlgroup which was higher than that of AA wild type gene. Carrying the rs4353 site of AG and GG genotypes of Uighur Medicine abnormal Hilit risk were 1.434 times and 1.275（95% CI: 1.073².210） with wild genotype of AA（95% CI: 1.146².989）. ACE gene rs807592 locus in the case group and the controlgroup were mainly to mutation genotype CC based, rs807592 locus T allele in the case group and the controlgroup composition were higher than those of the C allele, CT and CC mutation genotype in distribution in the case group and the controlgroup were higher than TT gene wild type. Rs807592 sites CT and CC carrying the mutant gene of the Uygur Medicine abnormal Hilit risk are carrying wild genotype TT the 3.555 times（1.793⁵.204） and 4.293 times（1.893⁷.717）; Carrying the mutant C allele of Uyghur Medicine abnormal Hilit risk were 2.702 times（1.647⁴.418） carry T wildlife gene.（2） ApoE gene rs405509 genotype in the case group and controlgroup were mainly AC genotype, carrying rate were 27.6% and 20.5%, AA, AC and CC three genotypes in cases and controls the overall distribution of the difference was not statistically significant（P>0.05）; Rs405509 allele in case group and in the controlgroup were mainly A mutation genotype and carrying rate were 33.6% and 23.8%, A allele in the case group and the controlgroup in which distribution is higher than that of C allele, the difference was statistically significant（χ²=4.012, P=0.045） C variant allele of Uighur Medicine abnormal body fluid quality risk is respectively 3.205 times（1.716⁵.631） with A wild allele. ApoE gene rs769450 locus in the case group and the controlgroup were mainly to mutation genotype GG mainly, A and G allele in the case group and controlgroup differences in the distribution of no statistical significance（P>0.05）. Rs769450 site AG and GG carrying the mutant gene of the Uygur Medicine abnormal Hilit risk respectively is carry wild genotype TT 0.301 times（0.137⁰.660） and 0.337 times（0.156⁰.727）.（3） The rate of ACE gene rs8075924 sites in abnormal blood quality and abnormal phlegmatic genotype and allelic clutter were higher than that of abnormal bile fluid abnormal bile fluid; ApoE gene rs405509 site and rs769450 sites in savda groups such as the heterozygosity rate were higher than abnormal sapra. There were linkage disequilibrium between the degree of ACE gene rs4293, rs4344, rs4353, rs4353 and rs4344 three loci, three rs4461142 loci. A A A* haplotype frequencies in the controlgroup than in the case group, carrying the A A A* haplotype in patients with abnormal body fluid risk was not a carrier of 0.552 times.4.Association of gene-gene and gene-environment interaction with the genetic susceptibility to abnormal body fluid（1） The fork of multiplicative interaction model based on the analysis, were screened out of three with statistical significance（P<0.05） gene- gene multiplication interaction, respectively, for the super multiplicative interaction effect between between ACE gene polymorphism rs4316818 and rs4353 times multiplicative interaction and rs4293 and rs4344; between AopE gene polymorphism rs405509 and rs769450 super multiplicative interaction effect. Individuals carrying rs4316818 CT+CC mutation genotype and rs4353 AG+GG mutation genotype in Uyghur Medicine abnormal humoral quality risk was also carrying rs4316818 wild genotype TT and rs4353 genes from the wild type AA risk of 3.839 times. Individuals carrying both rs405509 and AC+GG rs769450 genes are 3.190 times the risk of rs405509 and rs769450 wild-type AA risk of disease. Individuals carrying rs4293 and rs4344 AC+GG Uygur Medicine abnormal humoral risk 2.830 times while carrying rs4293 and rs4344 wild genotype AA risk, suggest that an individual while carrying rs4293 rs4344 mutant gene AG with risk factors, which may increases the risk of Uyghur Medicine abnormal Hilit（χ²=5.704, P=0.016）.（2） The fork of additive interaction model based on the analysis, we screened a total of three pairs with statistical significance（P<0.05） gene additive genetic interactions, respectively, for its positive additive interaction between ACE gene polymorphism rs4316818 and rs4461142 between（U=5.583, P=0.032）, rs405509 and rs4344 positive additive interaction（U=7.627, P=0.028）, rs4293 and rs4353 positive additive interaction（U=11.031, P=0.001）.When the individual also carry rs4316818 CT+CC allele and rs4461142 CT+CC, such as gene may increase dimensional Medicine abnormal Hilit danger; when the individual also carry rs405509 CT+CC allele and rs4344 CT+CC allele gene may increase dimensional Medicine abnormal Hilit danger; when the individual also carry rs4293 CT+CC allele and rs4353 CT+CC allele gene may increase dimensional Medicine abnormal Hilit danger. Rs4316818+rs4353+rs4293 three factor model was selected as the best model of gene gene interaction（P=0.035） by MDR analysis.（3） The fork of multiplicative interaction model based on the analysis, were screened out five pairs with statistical significance（P<0.05） gene diet interactions, respectively, for its ACE gene polymorphism of rs4316818 and milk fruit type of dietary pattern time multiplicative interaction, rs4293 and meat egg types dietary pattern time multiplicative interaction,rs4344 and milk fruit type of dietary pattern of excess multiplicative interaction and AopE gene polymorphism of rs405509 and eggs meat type of dietary pattern time multiplication interaction and rs769450 and unique dietary pattern of a multiplicative interaction.CT+CC rs4316818 genotype and dietary patterns for the high intake of fruit milk type of abnormal body fluid risk was to carry the TT rs4316818 genotype and dietary patterns for the 0.921 times of the low intake of fruits and milk type. Carry rs4293 AG+GG genotype and dietary pattern for high intake of meat and egg type of Uyghur Medicine abnormal Hilit risk is also carrying rs4293 AA genotype and diet pattern for low egg type meat intake were 3.708 times, suggesting that rs4293 mutation genotype AG and meat egg type high intake in dietary patterns were risk factors, the may increase dimensional Medicine abnormal Hilit risk（χ²=7.325, P=0.034）. Carry rs4344 CT+CC genotype and diet pattern for milk fruit type high intake are Uygur Medicine abnormal Hilit risk was also carrying rs4344 CT+CC genotype and dietary patterns for fruit milk type low intake 0.476 times. Carrying the rs405509 AC+CC genotype and dietary pattern for meat egg type high intake of Uighur Medicine abnormal Hilit risk is 2.372 times while carrying the rs405509 AA genotype and meat type low intake of eggs.Carrying rs769450 CT+CC genotype and dietary pattern for grain and vegetable high intake of Uyghur Medicine abnormal Hilit disease risk was also carrying rs769450 TT genotype and dietary pattern for grain and vegetable low intake of 0.812 times.（4） The fork of additive interaction model based on the analysis, we screened a total of three pairs with statistical significance（P<0.05） gene environment interaction on an additive scale, which were the ACE gene polymorphism of rs4316818 and milk fruit type of dietary pattern（U=6.306, P=0.022） and ACE gene polymorphism of rs4353 and eggs meat type of dietary pattern（U=5.958, P=0.029） and ACE gene polymorphism of rs4461142 and milk fruit type of dietary pattern（U=4.648, P=0.040）. It was possible to reduce the risk of abnormal body fluid when individuals carrying a CT+CC rs4316818 allele and a high dietary pattern for high intake of fruit and milk. It may increase the risk of abnormal body fluid when the individual carries the CT+CC rs4353 allele and was likely to increase dietary patterns for high intake of meat eggs. It was possible to reduce the risk of abnormal body fluid when individuals carrying a CT+CC rs4461142 allele and a high dietary pattern for high intake of fruit and milk.Rs769450+rs405509 +rs4353+rs4293+ five factor model was used as gene environment interaction model（P=0.045） by MDR analysis. Conclutions:（1） The overall prevalence of abnormal Hilit in women than men. Male and female in Uygur normal Hilit groups in blood matter, in abnormal Hilit group are mainly sawda. Abnormal Hilit group average age was higher than the normal Hilit group. Normal body fluid is more common in young and middle-aged people, abnormal body fluid was more common in the elderly population. According to the BMI and WHR two indicators of the normal rate of obesity in the body fluid was basically consistent, but the rate of abnormal body fluid was different, obesity rate WHR group is more accurate. The abnormal Hilit population than normal Hilit people susceptible to hypertension, which was mainly the abnormal savda phenotype of hypertension.The abnormal Hilit population than the normal Hilit populations were more likely to suffer from high blood pressure and high blood sugar.（2） The pattern of grain and vegetable diet was the main dietary pattern of Uygur. There were different levels of dietary patterns of male and female, urban and rural residents. The elderly were easy to choose the type of grain and vegetables and fruit milk type of dietary patterns, middle-aged people mainly choose the type of meat egg type meal mode, young people was easy to select the nuts type diet. The four dietary patterns of male and female were approximately the same in the abnormal body fluid, but the distribution was not the same in the individual dietary pattern. Men and women dietary patterns more abnormal savda distribution, but dietary pattern of some men there are abnormal savda and abnormal phlegmatic coexist as the phenomenon, female part of dietary patterns also exist abnormal savda and and abnormal blood quality coexistence phenomenon mainly. Fruit milk types of dietary patterns and MS and hypertension prevalence rate was negatively correlated, suggesting that the dietary patterns of fruits and milk may was a protective factor for MS and hypertension; meat egg type of dietary pattern and high fasting glucose and obesity was positively correlated, that meat high intake of dietary pattern may be impaired fasting glucose and obesity risk factors. Nuts type dietary pattern was negatively correlated with fasting glucose, suggesting that nuts are protective factors of high fasting blood glucose, it helps to lower blood glucose levels.（3） Mutations of ACE gene rs4353 may was the risk factors of Uygur Medicine Hilit Ag and GG genotypes, rs807592 mutation genotype CT and CC and rs807592 C mutation allele, its existence will increase the risk of Uyghur Medicine abnormal Hilit. ApoE gene rs405509 C mutant allele may be a risk factor for the body fluid, and its presence will increase the risk of abnormal body fluid. ACE gene rs8075924 locus genotypes, and genotype mutation was the cause of the major genetic factors for the formation of abnormal blood quality and abnormal phlegmatic;ApoE gene rs405509 sites and rs769450 sites such as gene mutations are the major genetic factor resulting in the formation of abnormal savda. Three SNPs loci rs4293, rs4344, rs4353 formed a total of 8haplotypes, A A A* haplotype was the protective factor, which could reduce the risk of abnormal Hilit in Uighur Medicine. Rs4461142, rs4344, rs4353, three loci were formed 8haplotypes, A A C* haplotype frequency is higher than the patients in the controlgroup, G G C* haplotype frequency in case group was higher than that of controlgroup. The risk of abnormal body fluid in patients with A C* A haplotype was 0.552 times that of non carriers, suggesting that the A C* A haplotype was the protective factor, which could reduce the risk of abnormal body fluid. The risk of abnormal body fluid in patients with G C* G haplotype was 4.293 times that of non carriers, suggesting that G C* G haplotype was a risk factor, and its presence would increase the risk of abnormal body fluid.（4） Between ACE gene polymorphism rs4316818 and rs4353 has a multiplicative interaction and suggest that an individual while carrying rs4316818 mutation genotype CT and rs4353 mutation genotype AG with risk factors, which may increases the risk of Uyghur Medicine abnormal Hilit; super multiplicative interaction between ACE gene polymorphism rs4293 and rs4344, suggest that an individual while carrying rs4293 rs4344 mutant gene AG with risk factors and it may increases the risk of Uyghur Medicine abnormal Hilit; Between AopE gene polymorphism rs405509 and rs769450 with super multiplicative interaction and suggest that an individual while carrying rs405509 rs4353 mutation genotype AC with risk factors, which may increases the risk of Uyghur Medicine abnormal Hilit. Between ACE gene polymorphism rs4316818 and rs4461142 with positive additive interaction, indicating that when individual also carry rs4316818 CT+CC allele and rs4461142 CT+CC, such as gene may increase dimensional Medicine abnormal Hilit danger; AopE gene polymorphism of rs405509 and ACE gene rs4344 with positive additive interaction, when the individual also carry rs405509 CT+CC allele and rs4344 CT+CC etc. gene may increase dimensional Medicine abnormal Hilit danger; ACE gene polymorphism between rs4293 and rs4353 has a positive additive interaction, when the individual also carries the CT+CC rs4293 allele and CT+CC rs4353 allele may increase the risk of abnormal body fluid. When the ACE gene polymorphism rs4316818, rs4353, rs4293 three sites together, it will increase the risk of abnormal body fluid.A multiplicative interaction between ACE gene polymorphism and rs4316818 fruits and milk dietary patterns, suggesting that rs4316818 mutant gene CT and high intake of fruits and milk type dietary pattern as a protective factor, which may reduce the risk of abnormal Hilit in Uighur Medicine; a multiplicative interaction between ACE gene polymorphism and rs4293 egg type meat dietary pattern the rs4293 mutant gene AG and meat egg type high intake of dietary patterns as risk factors, which may increase the risk of abnormal Hilit in Uighur Medicine; ACE rs4344 gene polymorphism and dietary pattern of fruit milk type super multiplicative interaction, suggesting that rs4344 mutant gene CT and high intake of fruits and milk type the dietary pattern was the protective factor, which may reduce the risk of abnormal Hilit in Uighur Medicine; AopE gene polymorphism of rs405509 and eggs meat type of dietary pattern of multiplicative interaction, suggesting that rs405509 mutation genotype CT and high intake of meat and egg type diet pattern for risk factors, which may increase the risk of Uyghur Medicine abnormal Hilit; AopE gene polymorphism of rs769450 and the specific type of dietary pattern of multiplicative interaction, suggesting that rs769450 mutation genotype CT and high intake of specific dietary pattern is a protective factor, which may will reduce the risk of Uyghur Medicine abnormal Hilit. When individuals carrying rs4316818 CT+CC allele and a high intake of fruit milk type high intake of dietary pattern may be risk reducing the incidence of Uyghur Medicine abnormal Hilit of negative interaction of ACE gene polymorphism of rs4316818 and milk fruit type of dietary pattern; ACE gene polymorphism of rs4353 and eggs meat type of dietary pattern of positive interaction, when individuals carrying rs4353 CT+CC alleles and high intake of meat and egg type dietary pattern may increase dimensional Medicine abnormal Hilit danger; ACE gene polymorphism of rs4461142 and fruit milk type dietary pattern of negative interaction, when individuals carrying rs4461142 CT+CC allele and a high intake of fruit milk type high intake of dietary pattern may be risk reducing the incidence of Uyghur Medicine abnormal Hilit. When the ACE gene polymorphism rs4353, rs4293 loci and AopE gene polymorphism rs769450, rs405509 and meat egg type dietary pattern, it will increase the risk of abnormal body fluid.