Purine Metabolism Enzyme SNP to Uric Acid Production

Study Overview
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Brief Summary
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Determine whether a relationship exists between polymorphisms of the genes XDH, HPRT1, and PRPS1 and gout, hyperuricemia, or the dose of xanthine oxidase (XO) inhibitors to reach a goal serum uric acid of less than 6 mg/dL. This study is observational in nature as no dose adjustment of XO inhibitors will be made by study investigators.

Detailed Description
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Background: Our recent gout study demonstrated a relationship between the xanthine oxidase (XO) single nucleotide polymorphism (SNP) 2107A>G to the dose of allopurinol needed to reach a goal serum uric acid level of 6 mg/dL or less. This study had some limitations but suggests that specific SNPs could be related to dose of allopurinol needed to treat. Objective: To determine the relationship of multiple purine enzyme SNPs of genes encoding PRPS1, HPRT1, and XO to the dose of xanthine oxidase inhibitor needed to achieve a goal treatment uric acid level of less than 6 mg/dL. Another primary outcome will be to determine relationship of two XO SNPs to hyperuricemia/gout. A secondary outcome will be to determine the frequency of these SNPs tested. Design: Patients will be consented for enrollment in either the gout/hyperuricemia group or a control group. Control group patients will have neither gout nor hyperuricemia. No patients will be enrolled if they are overproducers of uric acid. It is anticipated that 200 patients will be enrolled in each group for a total of 400 patients over the next 2 years.

Official Title
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Relationship of Purine Metabolism Enzyme Single-Nucleotide Polymorphisms to Uric Acid Production and Response to Xanthine Oxidase Inhibitors

Conditions
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Gout, Hyperuricemia

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The study will be open to all adults over age 18 years of age who satisfy at least one of the conditions below: Have asymptomatic hyperuricemia (serum uric acid level > 7.0 mg/dL) on at least 2 separate occasions, Clinical diagnosis of gout, Have neither asymptomatic hyperuricemia or gout but will serve as part of the control group (approximate age/gender matched control) Exclusion Criteria: To best isolate the relationship between purine enzyme SNPs to hyperuricemia or gout and its treatment, factors which could elevate the serum uric acid level independent of protein function need to be excluded. Specifically, patients who are overproducers of serum uric acid will be excluded: Have a myeloproliferative disorder (hematologic malignancy such as leukemia or lymphoma) Are actively receiving therapy for any neoplasia (aside from non-melanoma skin cacner) Have greater than 5% of skin involvement from psoriasis Have a known history of xanthinuria Consume more than 14 drinks per week of alcoholic beverages Patients that are pregnant or nursing will not be enrolled. Patients to be enrolled in the control group will also be excluded from enrollment if they have any of the conditions above.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Gout/Hyperuricemia<br>Subjects with a diagnosis of hyperuricemia (defined as a uric acid of > 7.2 mg/dl) and/or gout. | |
| Control<br>Approximate age and gender matched controls without hyperuricemia or gout | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relationship of SNPs to gout, hyperuricemia, and dose of xanthine oxidase inhibitor needed to reach goal serum uric acid level of < 6 mg/dL. | This study will test the relationship of 2107A>G XO to the dose of allopurinol needed to achieve a treatment goal of less than 6 mg/dL. It will also test whether or not SNPs affecting the gene for hypoxanthine phosphoribosyltransferase 1 (HPRT1) are related to gout, hyperuricemia, or the dose of XO inhibitor needed to reach a goal of 6 mg/dL. Relationships will be determined using typical non-parametric or parametric tests depending on the skew and skedasticity. - Determine the relationship of several SNPs in genes encoding HPRT1 and one XO SNP (2107A>G) to the dose of xanthine oxidase inhibitor needed to achieve a goal treatment uric acid level of less than 6 mg/dL. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine frequency of SNPs tested | (1) Measure minor allele frequency of all SNPs tested as the number of heterozygotes present in the population recruited divided by the total number of patients recruited. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Xanthine Oxidase, Gout, Hyperuricemia, SNP, Single Nucleotide Polymorphisms