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| Name | Class |
|---|---|
| United States Air Force | FED |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Gout/Hyperuricemia | Subjects with a diagnosis of hyperuricemia (defined as a uric acid of > 7.2 mg/dl) and/or gout. | ||
| Control | Approximate age and gender matched controls without hyperuricemia or gout |
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| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Determine relationship of XO SNP 2107A>G and several HPRT1 SNPs to hyperuricemia/gout. | 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 relationship of XO SNP 2107A>G and several HPRT1 SNPs to hyperuricemia/gout. |
Inclusion Criteria:
Exclusion Criteria:
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.
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Patients for either the gout/hyperuricemia group or the control group will be recruited at the time of their evaluation in either the Internal Medicine (IM) Clinic or IM Specialties Clinic.
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| Name | Affiliation | Role |
|---|---|---|
| Matthew B Carroll, MD | Keesler Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Keesler Medical Center | Keesler Air Force Base | Mississippi | 39564 | United States |
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| ID | Term |
|---|---|
| D006073 | Gout |
| D033461 | Hyperuricemia |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D000070657 | Crystal Arthropathies |
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DNA will be banked for future studies as allowed by patient consent
| 2 years |
| D012216 |
| Rheumatic Diseases |
| D011686 | Purine-Pyrimidine Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |