Study On The Relationship Between ABCG2 Functional Single Nucleotide Polymorphisms And Gout And Hyperuricemia And The Establishment Of Workers With Hyperuricemia

The prevalence of gout and hyperuricemia over the world is increasing due to improved quality of human life over the past decades. Therefore, It has been highly focused on by scientists throughout the world, especially on the tremendous developments of pathogenesis and treatment. Among these developments, studies on certain genetic basis had showed that took actions on the pathogenesis as well as acquired factors e.g. dieting, alcohol intake, obesity, etc.Besides studies of basic medicine regarding gout and hyperuricemia, we have also come to realize that early recognition and long-term management are critical for hyperuricemia patients.However, no consensus or guidelines have been developed for the general management of hyperuricemia. And most relevant studies are cross-sectional, which are limited to some extent. Based upon all these above, we believe that establishing a prospective cohort study is of great importance for the management and treatment of hyperuricemia.Objectives:1) Investigating the relationships between SNP rs2231142, SNP rs72552713and the prevalence of gout and hyperuricemia, by way of comparing three groups:gout patients, hyperuricemic patients and people with normal serum uric acid.2) Establishing cohorts of hyperuricemic patients and control based on the cohorts of physical emamination for staff of PUMCH.Methods:1) Gout group has been set up based on gout patients from gout clinic and inpatients of general medicine department of PUMCH, and normal control group and hyperuricemia group have been set up with staff of PUMCH participating physical examinations. We detected the genotypes of rs2231142and rs72552713with bi-primer and tetra-primer ARMS-PCR method. Through regression analysis we studied the distribution of the genotypes of rs2231142、rs72552713and relationship between correspondent A,T alleles and occurrence of gout and hyperurecimia. 2) Of all staff participating physical examination of PUMCH, we established hyperuricemia and control groups. We conducted elaborate history taking and systematic lab tests to set up baseline for these subjects, including routine lab tests, imaging exams, constitutional testing, echocardiography, carotid ultrasound, bone density exam, pulmonary function tests, etc, and comprehensively gathered past medical history, medication use history, life style, diet habits, etc, by means of questionnaires.Results:1) The study enrolled147gout patients,171hyperuricemic patients,321control subjects, with639subjects in total. Of all the subjects, allele A has a frequency of36.6%. Difference of gene frequency of allele A between gout and hyperuricemia groups and control group proved significant (37.4%and27.1%respectively, p<0.01). Allele A is significantly related with the occurrence of gout and hyperuricemia, OR=3.23(95%CI:2.31-4.51, p<0.01). Compared with CC genotype, CA and AA genotypes come with an OR of2.83(95%CI:2.00～4.01,p<0.01) and5.84(95%CI3.29～10.4, p<0.01) respectively, regarding the occurrence of gout and hyperuricemia. With gender, age, blood lipids, blood pressure and blood glucose levels adjusted, relative risk of allele A regarding hyperuricemia is3.67(95%CI2.15-6.26, p<0.01). However, in comparison between gout and hyperuricemia groups, allele A hasn’t significantly increased the risk of occurrence for gout. Allele T has a frequency of0.95%in general subjects. When comparing gout and hyperuricemic groups with control group, we found that allele T brought about a risk of11.5(95%CI:1.47-89.3, p<0.01).2) Population study enrolled2270subjects of PUMCH staff participating physical examination, with a male to female ratio of687:1583. We found221subjects with hyperuricemia, with a detection rate of13.2%, among whom there were111males and110females, with detection rates of20.9%and9.6%respectively. Compared with the cross-sectional study of hyperuricemia and other metabolic abnormalities in PUMCH staff conducted by our department, after adjustment of age, sex, BMI, blood lipids and blood pressure, hyperuricemia still increases the risk of new-onset hyperglycemia and hypertriglyceridemia. Moreover, we enrolled the273subjects, who were segmentally matched by sex and age, into the hyperuricemia and control cohorts, conducting a systematic baseline evaluation, and establishing a long-term follow-up mechanism.Conclusion:1) Comparing gout and hyperuricemia groups with control, genotypes AA, CA and allele A of SNP rs2231142all increases the risk of occurrence of gout and hyperuricemia. Comparing gout with hyperuricemia groups, genotype AA is significantly related to the occurrence of gout, while genotype CA and allele A are not significantly related so. Genotype CT and allele T of SNP rs72552713is significantly related to the occurrence of gout and hyperuricemia, bearing which, gout patients feature early onset, frequent episodes in early course of disease and multiple joint involvement. The combined analysis of SNP rs2231142and SNP rs72552713allows for a preliminary assessment of ABCG2function and further indicates the risk of early-onset gout.2) The health check of PUMCH staff in2014showed no significant change in terms of the prevalence of hyperuricemia, compared with the results in2008; but higher than the results from similarly-sized cohort studies in this country. Hyperuricemia proves to be correlated with other metabolic abnormality, i.e. hyperglycemia and hypertriglyceridemia.We have established a hyperuricemia cohort and its control cohort, built a foundation for the further study of hyperuricemia and other metabolic disorders.