Relationship of Purine Metabolism Enzyme Single-Nucleotide Polymorphisms to Uric Acid Production and Response to Xanthine Oxidase Inhibitors
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Relationship of SNPs to gout, hyperuricemia, and dose of xanthine oxidase inhibitor needed to reach goal serum uric acid level of < 6 mg/dL.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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)
排除标准
- •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.
结局指标
主要结局
Relationship of SNPs to gout, hyperuricemia, and dose of xanthine oxidase inhibitor needed to reach goal serum uric acid level of < 6 mg/dL.
时间窗: 2 years
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.
次要结局
- Determine frequency of SNPs tested(2 years)