Primary Hyperuricemia Correlated Genic And Environment Factors And Relationship With Metabolic Diseases

Uric acid an end product of purine metabolism, is degraded in most mammals by the hepatic enayme and urate oxidase (uricase), to allantion which freely in the urine. Usually, the pool size of urate for an adult male is about 1,200 mg, and 700 mg urate is produced daily. The production is balanced by the excretion of urate into urine (500 mg) and intestine (200 mg). The hyperuricemia occurs if this balance is disturbed, Some human subjects have various abnormalities in urate metabolism. According to the mechanisms, hyperuricemia is classified into two different types, overproduction and underexcretion. Overproduction is caused by some enzymatic abnormalities, such as PRPP synthetase superactivity, HPRT deficiency et al .Study show that it still can be caused by genetic defects, such as the superactivity of Angiotensin Converting Enzyme Gene (ACE), angiotensin-coverting enzyme gene (AGT),Beta 3-adrenergic receptor gene, Methylenetetrahydrofolate reductase, MTHFR (C677T) gene defects. Underexcretion of urate is caused by renal insufficiency and genetic defects, for example. The Human Urate Transporter gene, ApoE gene, Leptin gene were cinsidered the correlation with hyperyricemia.Many studies showed that primary hyperuricemia was a complx genetic traits caused by mutiple genetic and environmental components. The correlated environmental factors include diet, life style, culture, occupation and economy level et al. A number of studies have shown that serum uric acid (SUA) plays a role in the development of cardiovascular morbidity in the general population, as well as in patients with hypertension, type II diabetes, and cardiac or vascular diseases.Many ethnicities were lived in XingJiang, and the Han and Uygur ethnicity were the main in all population,they came from different genetic background ,different life mode and diet habit. In the present study, we investigated uria acid level and the prevalence of primary hyperuricemia in Han and Uygur ethenicity. Furthermore used PCR and gene chip technic to clarify the relationship between gene polymorphism and primary hyperuricemia in Han and Uygur ethnicity.Finaly via Logistic regression to found the related factors that related genetical and environment and to determine wither primary hyperuricemia corrected with other metabolic diseases.Objectives:1. Rreveal the uric acid level of Han and Uygur ethnicity and find the prevalence and the rule of primary hyperuricemia of two ethnicities in Xinjiang.2. Analyze the correlation of gene SNP and primary hyperuricemia in Han and Uygur ethnicity in Xinjiang.3. Found the correlated factors of genic and environment with primary hyperuricemia between Han and Uygur ethnicity in Xinjiang4. Reveal the relationship of primary hyperuricemia and Metabolic Diseases.Contents and MethodsIn the present study, we first investigated uria acid level and the prevalence of primary hyperuricemia in Han and Uygur ethenicity. Furthermore used the Multiplex Amplification Refractory Mutation System Polymerase Chain Reaction (Multi-ARMS PCR), Restriction Fragment Length Polymorphism Polymerase Chain Reaction (PCR-RFLP) and gene chip technic to clarify the relationship between gene polymorphism and primary hyperuricemia in Han and Uygur ethnicity. A questionnaire including family history of disease, lifestyle-related variables and other factors which may be corrected with primary hyperuricemia was used to every participants.The questionnaires were discussed during physical examinations. Finaly via Logistic regression to found the related factors that related genetical and environment and to determine wither primary hyperuricemia corrected with other metabolic diseases. Analysis the correlated Genic and Environment Factors of primary Hyperuricemia and relationship with Metabolic Diseases.Results:1 Uric Acid Level and Prevalence of Primary hyperuricemia in Hanand Uygur Ethnicity(1)Han ethnicity SUA level was was higher than Uygur ethnicity and man was higher than womanin (P<0.05). (2)The average age of primary hyperuricemia occered of Han was 38.01 in man and 42.07 in woman, Uygur ethnicity was 44.92 in man and 50.00 in woman. The prevalence of primary hyperuricemia Han ethnicity was Han ethnicity was higher than Uygur ethnicity (P<0.05) and man was higher than womanin (P<0.05). (3)The uric acid level were increased accompanying the age growing in two ethnicities. Between different age groups, uric acid level were different in two ethnicities (P<0.05).These differnences show statistically significant (P<0.05). But the increase trend in man was not bigger than in woman. (4)Accompany with ages growing, the prevalence of primary hyperuricemia of Han and Uygur ethnicity were increased (P<0.05). But except man in Han ethnicity was decreased, man in Uygur ethnicity did not show rule , the woman in two ethnicities,were increased, they all show statistically significant (P<0.05).2 The Gene Single Nucleotide Polymorphism (SNP) of Primary Hyperuricemia in Han and Uygur Ethnicity2.1 Underexcretical Primary Hyperuricemia Related Gene SNP Aanalysis2.1.1 Relationship between Apolipopritein E gene SNP and Primary Hyperuricemia(1)The distribution of Apolipoprotein E gene type in Han and Uygur ethnicity were significant differences (P<.05). Among the six genotypes of Apolipopretein E gene, E3/3 was the most common one in two ethnicities. E2/2 gene frequency were larger than E4/4 in Han ethnicity, but E4/4>E2/2 in Urger ethnicity. (2)The allele gene frequency ofε2,ε3,ε4 in Han were 0.224, 0.688 and 0.067 and 0.245, 0.615, 0.14 in Uygur ethnicity. Theε3 allele gene was the most one in two ethnicities, same as the common people in world. Compared with normal group,ε2 allele gene frequency was decreased andε4 was increased in primary hyperuricemia group of two ethnicities. (3) The SUA and other biochemical criterion in Apolipoprotein E allele genes showed different rule in two ethnicities.(4) The serum of uric acid and plasma lipid parameters in hyperueicmia group were higher than the normal group in Han and Uygur ethnicity in different allele gene (P<0.05).but still showed difference in two ethnicities.(5) hyperuricemia groupε4 allele frequency in Han ethnicity was similar to Asian, but in Uygur ethnicity was closed to people Europe and American.2.1.2 Relationship between Leptin Gene G2548A Polymorphism and Primary Hyperuricemia(1) The AA,AG,GG allele frequency of Leptin gene G 2548A in Han were 0.541, 0.374 and 0.085,in Uygur ethnicity were 0.497, 0.415 and 0.088.(2) The AA allele frequency of leptin G2548A was significantly higher and AG,GG were lower in hyperuricemia group than the normal group (P<0.05). (3) The relative risk of primary hyperuricemia of AA+AG gene type was 0.625 times (OR=0.625; 95%CI=0.285-1.368) to GG gene type in Han and 0.478 times (OR=0.478, 95%CI=0.103-2.213) in Uygur ethnicity, but not insignificence between primary hyperuricemia and normal groups in two etnicities (P>0.05). (4) In Han ethnicity, the AA+Ag gene type, Compared to normol group, hyperuricemic group uric acid and other plasma lipid parameters except the BUN were higher than the normal group in Han ethnicity ,were stastisignificence (P<0.05), but in GG gene type only the SUA was higher than normal, was stastisignificence (P<0.05) In Uygur ethnicity, Compared to normol group, the AA+Ag gene type hyperuricemicl group uric acid and other plasma lipid parameters except the seurm leptin and FBS level, were higher than the normal group, and have stastisignificence (P<0.05).2.2 Overproductical Primary hyperuricemia Related Gene SNP Analysis(1)The frequency of MTHFR T allele amone the cases was significantly higher than the controls (P<0.05), the odds ratios for primary hyperuricemia was 1.617. UA, TG concentrations and body mass index were remarkabley higher in subjects with TT gene type than in subjects with CC gene type (P<0.05). (2)The SUA, BMI and TG level in MTHFR gene type C/C, C/T, T/T were increased, T/T and C/C gene type was significantly (P<0.05), other plasma lipid parameters, for example, WHR, SBP, DBP, TC, LDL-C, VLDL-C were increased two, and BUN, SCR, HDL-C decreased, but between the different gene types were insignificantly(P>0.05).(3)The frequency ofβ3-AR T964A gene type and allele between the cases and the controls was insignificantly(P>0.05), wen can not sayβ3-AR Trp64Arg mution was the risk of primary hyperuricemia.The large samples andprospective study to find the relationship of this mution and primary hyperuricemia.(4)The frequency of ACE I/D and AGT T704C gene type and allele between the cases and the controls was insignificantly (P>0.05) too.3 Primary Hyperuricemia Correlated Genic and Environment Factors and Relationship with Metabolic Diseases(1) Multivariate logistic regression analyses for influence of primary hyperuricemia shown nationality ,FINS, Hypertriglyceridemia, Hypercholesterolemia, BMI, serum Leptin, hypercholesterolemia, hypertriglyceridemia, low HDL cholesterol, diabetes, hypertension occupation(commerce) ,like drinking broth and chicken soup may be the risk factors of primary hyperuricemia. Like eating muscle,drinking milk may be the protective facyors of primary hyperuricemia,Han has 2.697- fold in increased risk of primary hyperuricemia than Uygur. (2)Univariate regression analyses found that the relationship with uric acid were FINS, DBP, SBP, BMI, WHR, CREA, BUN, TG, HDL-C, LDL-C and VLDC-C in Han people. AGE, DBP, SBP, BMI, WHR, SCR, TG, TC, HDL, LDL-C and VLDC-C in Uygur (P<0.05). (3) Compared with normal group, except LDL-C, other biochemical criterion were higher than normal groupof Han people,but only SUA,SBP,DBP,BMI,WHR,FINS,SCR,TG,VLDL-C, have stastisignificence (P<0.05).In Uygur,except HDL-C,other biochemical criterion SUA,SBP,DBP,Serum leptin,BMI,WHR,FINS,CREA,TG,VLDL-C were higher than mormal group, have stastisignificence (P<0.05); Between normal groups in two ethnicities, the SUA,BMI,WHR,FINS,Serum leptin level in Uygur were higher than Han people(P<0.05); between hyperuricamia groups in two ethnicities, the BMI,Serum leptin level in Uygur were higher than Han people, but SCR,HDL-C level were lower than Han people (P<0.05). (4) From low to the high uric level group, except the Leptin and FBS , HDL-C has the decresed trend ,other biochemical criterions were increased in Han and Uygur ethnicity (P<0.05). The prevalence of obesity, Hypertension, Diabetes mellitus, hypertriglyceridemia, hypercholesterolemia, hypertriglyceridemia combination hypercholesterolemia and metabolic syndyome have the increasing trend when SUA level increasing, but only the prevalence of obesity, hypertriglyceridemia has significantly (P<0.05) in Han people,however in the Uygur ethnic,except the Diabetes mellitus,other diseases were significantly (P<0.05) too in different uria acid level groups. (5) Compared with normal group, the primary hyperuricemia group, the prevalence of obesity, hypertriglyceridemia, hypertriglyceridemia combination hypercholesterolemia and metabolic syndyome in Han people had the increasing trend (P<0.05). The Odds ratios of obesity, hypertriglyceridemia, hypertriglyceridemia combination hypercholesterolemia and metabolic syndyome in the presence of primary hyperuricemia were 2.362-times, 3.812-times, 3.163-times, 0.924-times and 4.971-times to SUA normal group. In about Uygur people, the prevalence of obesity, Hypertension, hypertriglyceridemia, hypercholesterolemia, hypertriglyceridemia combination hypercholesterolemia and metabolic syndyome in Han people had the increasing trend (P<0.05). The Odds ratios of these diseses were 3.626-times, 2.593-times, 1.905-times, 3.403-times, 4.016-times and 2.575-times to normal group. ConclusionThe uric acid level and prevalence of primary hyperuricemia were different in Han and Uygur ethnicity and sexes. Han were higher than Uygur ethnicity, man was higher than woman. Logistic regression analyses found tha tnationality, FINS, Hypertriglyceridemia, Hypercholesterolemia,BMI,serum Leptin, hypercholesterolemia, hypertriglyceridemia, low HDL cholesterol, diabetes, hypertension occupation (commerce), like drinking broth and chicken soup may be the risk factors ,and eating muscle, drinking milk, may be the protect factors of primar y hyperuricemia. Related Gene SNP Analysis found theε4 allele gene of ApoE gene , A allele of leptin G2548A and MTHFR T allele may be a genetic factor that may contribute to individual susceptibility for primary hyperuricemia. In the main while,Hyperuricemia were corrected with obesity, hypertriglyceridemia, hypertriglyceridemia combination hypercholesterolemia and metabolic syndyome et al matsbilc diseases. It is suggested that primary hyperuricemia was a component of metabolic syndrome and often accompanied by obesity, hypertension, hyperlipidemia, glucose intolerance, and cardiovascular risk factor clustering.In conclusion, primary hyperuricemia was a complx genic traits caused by mutiple genetic and environmental components. And corrected with matablic diseases.