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Genes that May Affect Uric Acid Levels

Written by Ana Aleksic, MSc (Pharmacy) | Last updated:
Nattha Wannissorn
Puya Yazdi
Medically reviewed by
Nattha Wannissorn, PhD, Puya Yazdi, MD | Written by Ana Aleksic, MSc (Pharmacy) | Last updated:

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Genes that May Affect Uric Acid Levels

Research Limitations

With the exception of some rare genetic diseases, these genes and their respective SNPs have only been associated with uric acid levels.

That does not mean having them will necessarily make you more likely to have how or low uric acid levels. More work is needed before we determine whether and how much they may increase a person’s risk of abnormal uric acid status.

It’s equally important to note that just because certain genotypes are associated with a disease, it doesn’t necessarily mean that everyone with that genotype will actually develop the disease! Many different factors, including other genetic and environmental factors, can influence the risk of gout and other diseases.

SLC2A9 Gene – The Absorptive Urate Transporter

The SLC2A9 gene encodes the glucose transporter 9 protein (GLUT4). It transports fructose and aids in the reabsorption of filtered urate by proximal tubules in the kidney. Loss-of-function mutations in this gene can cause hereditary hypouricemia due to reduced urate absorption [1].

The following SNPs in this gene have been studied:

  1. RS10017674
  2. RS10018204
  3. RS1014290 – The “G” allele was associated with a lower age at onset of Parkinson’s disease [2]. Individuals with the TT genotype had higher blood uric acid levels after increasing their consumption of soft drinks [3]. The GG genotype was associated with higher serum uric acid levels when compared with the TT/TG genotypes [4].
  4. RS1079128
  5. RS10805346
  6. RS11722228 – The “T” allele was linked to higher blood uric acid levels in females compared to males [5].
  7. RS12498150
  8. RS12498742 – Each copy of the minor “G” allele was linked with reduced risk of gout [6].
  9. RS12498956
  10. RS13103879
  11. RS13129697 – The “C” allele was linked to lower blood urate levels in the Croatian population [7].
  12. RS13131257 – The “T” allele was associated with lower blood uric acid levels in Mexican Americans [8].
  13. RS13328050
  14. RS16868246
  15. RS16890979
  16. RS17185835
  17. RS17185870
  18. RS1850744
  19. RS2018643
  20. RS3733585 – The “G” allele was associated with cleft palate [9].
  21. RS3733591 – The “C” allele was linked with an increased risk of severe gout for some populations [10].
  22. RS3775948 – The “G” allele was associated with an increased risk of gout [11].
  23. RS4311316
  24. RS4312757
  25. RS4314284
  26. RS4339211
  27. RS4455410
  28. RS4473653
  29. RS4475146 – The “A” allele was associated with gout [12].
  30. RS4481233
  31. RS4519796
  32. RS4580649
  33. RS4621431
  34. RS6449157
  35. RS6449159
  36. RS6449171
  37. RS6449172
  38. RS6449174
  39. RS6449176
  40. RS6449178
  41. RS6449201
  42. RS6449213 – This variant was associated with higher blood urate levels [13].
  43. RS6814664
  44. RS6815001
  45. RS6823361
  46. RS6832439 – The “A” allele was associated with decreasing blood uric acid levels [14].
  47. RS6834893
  48. RS6836706
  49. RS6838021
  50. RS6839490
  51. RS6843873
  52. RS6844316
  53. RS6849729
  54. RS6852441
  55. RS6855911 – The “G” allele was associated with less uric acid [15].
  56. RS733175
  57. RS734553 – The “T” allele was associated with gout [16].
  58. RS737267 – The GG genotype was associated with 1.25 times higher risk of gout [17].
  59. RS7376948
  60. RS7378305
  61. RS7378340
  62. RS7435196
  63. RS7442295 – The more common “A” allele is associated with higher blood urate levels and hyperuricemia [18].
  64. RS7658170
  65. RS7671266
  66. RS7672947
  67. RS7676733
  68. RS7677710
  69. RS7680126
  70. RS7686538
  71. RS938554
  72. RS9993410
  73. RS9994266

More research is needed to verify these associations, which are still largely experimental.

ABCG2 Gene – The Multi-functional Transporter that Exports Urate

The ABCG2 gene encodes a multifunctional transporter that belongs to the ATP-binding cassette family and controls the export of various compounds including urate using ATP [19].

Limited studies suggested the following associations, which have yet to be confirmed in large-scale investigations:

  1. RS13120400
  2. RS1481012 – The “A” allele was associated with an increased risk of gout [12]. Heterozygous carriers of the minor allele “G” had a lower risk of colorectal cancer in one small study [20].
  3. RS17731538
  4. RS2199936 – The “A” allele was associated with incident gout [21].
  5. RS2231137 – The T” (minor) allele was associated with an increased risk of tophaceous gout [22], which causes joint pain and arthritis.
  6. RS2231142 – The T (minor) allele was associated with an increased risk of gout [23].
  7. RS2728124
  8. RS2728125 – The “G” allele was associated with gout [11].
  9. RS3114018
  10. RS4148152
  11. RS4148155
  12. RS72552713 – The “A” allele was associated with an increased risk of gout [24].

SLC22A12 Gene – The Urate Transporter That Determines the Amount of Urate Present in the Blood

The SLC22A12 gene encodes a protein that is a member of the organic anion transporter (OAT) family, and it transports urate. Found in the epithelial cells of the proximal tubule of the kidney, this protein helps control the amount of urate present in the blood.

This gene is thought to be the major luminal pathway for urate reabsorption in humans and mutations have been associated with raised blood urate levels and decreased fractional urate excretion in limited studies [25].

  1. RS12800450 – The “T” allele was associated with reduced blood urate levels [26].
  2. RS505802 – The “A” allele was associated with gout arthritis in Han Chinese males [27].

SLC22A11 Gene – The Organic Anion Transporter That Reabsorbs Uric Acid

The SLC22A11 gene encodes a protein that is involved in the transport and excretion of organic anions. It also aids in the reabsorption of uric acid on the apical membrane of the proximal tubule in the kidneys [28].

  1. RS17300741 – The minor “G” allele was associated with lower blood uric acid levels in women [29].

SLC17A1 Gene – The Renal Urate Exporter

The SLC17A1 gene encodes a sodium-dependent transporter that helps transport glucose and other sugars, bile salts and organic acids, metal ions and amine compounds, as well as urate. It was also associated with a higher risk of gout and hyperuricemia in some studies, but more research is needed [30].

  1. RS1165196 – The allele “C” was associated with an increased risk of gout in patients with normal uric acid excretion [31]. It was also associated with a low-/high-density lipoprotein cholesterol ratio [32].
  2. RS1183201 – The minor “A” allele was associated with a reduced risk of gout in European and western Polynesian populations [33].

SLC17A3 Gene – Transporter That Transports Intracellular Urate Out of the Cell

The SLC17A3 gene encodes a voltage-driven transporter that transports intracellular urate and organic anions from the blood into kidney tubule cells [34].

RS1165205 – The “A” allele was associated with higher blood uric acid levels [35].

UMOD Gene: The Protein That Helps Control The Amount of Water in Urine

The UMOD gene encodes uromodulin, a protein that is highly abundant in urine under physiological conditions. Defects in this gene are associated with various kidney diseases including glomerulocystic kidney disease with hyperuricemia [36].

  1. RS12444268 – The “A” allele linked to Type 1 Diabetes [37].
  2. RS12917707 – The minor “T” allele was associated with a lower risk of chronic kidney disease [38].
  3. RS13333226 – The minor “G” allele was associated with a lower risk of hypertension [39].
  4. RS4293393 – The “T” allele was associated with kidney stones and chronic kidney disease. This SNP may also be associated with susceptibility to gout, hypertension, and diabetes, but far more research is needed [40].

HPRT1 Gene – The Enzyme That Recycles Purines

This gene encodes hypoxanthine phosphoribosyltransferase 1, an enzyme that allows cells to recycle purines. Mutations in this gene have been associated with gout or Lesch-Nyhan syndrome [41].

PRPS1 Gene – The Enzyme That Helps Make Purines

The PRPS1 gene encodes an enzyme called phosphoribosyl pyrophosphate synthetase 1, or PRPP synthetase 1. This enzyme helps produce phosphoribosyl pyrophosphate (PRPP), which is involved in making purine and pyrimidine nucleotides [42].

About the Author

Ana Aleksic

Ana Aleksic

MSc (Pharmacy)
Ana received her MS in Pharmacy from the University of Belgrade.
Ana has many years of experience in clinical research and health advising. She loves communicating science and empowering people to achieve their optimal health. Ana spent years working with patients who suffer from various mental health issues and chronic health problems. She is a strong advocate of integrating scientific knowledge and holistic medicine.

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