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:
- RS10017674
- RS10018204
- 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].
- RS1079128
- RS10805346
- RS11722228 – The “T” allele was linked to higher blood uric acid levels in females compared to males [5].
- RS12498150
- RS12498742 – Each copy of the minor “G” allele was linked with reduced risk of gout [6].
- RS12498956
- RS13103879
- RS13129697 – The “C” allele was linked to lower blood urate levels in the Croatian population [7].
- RS13131257 – The “T” allele was associated with lower blood uric acid levels in Mexican Americans [8].
- RS13328050
- RS16868246
- RS16890979
- RS17185835
- RS17185870
- RS1850744
- RS2018643
- RS3733585 – The “G” allele was associated with cleft palate [9].
- RS3733591 – The “C” allele was linked with an increased risk of severe gout for some populations [10].
- RS3775948 – The “G” allele was associated with an increased risk of gout [11].
- RS4311316
- RS4312757
- RS4314284
- RS4339211
- RS4455410
- RS4473653
- RS4475146 – The “A” allele was associated with gout [12].
- RS4481233
- RS4519796
- RS4580649
- RS4621431
- RS6449157
- RS6449159
- RS6449171
- RS6449172
- RS6449174
- RS6449176
- RS6449178
- RS6449201
- RS6449213 – This variant was associated with higher blood urate levels [13].
- RS6814664
- RS6815001
- RS6823361
- RS6832439 – The “A” allele was associated with decreasing blood uric acid levels [14].
- RS6834893
- RS6836706
- RS6838021
- RS6839490
- RS6843873
- RS6844316
- RS6849729
- RS6852441
- RS6855911 – The “G” allele was associated with less uric acid [15].
- RS733175
- RS734553 – The “T” allele was associated with gout [16].
- RS737267 – The GG genotype was associated with 1.25 times higher risk of gout [17].
- RS7376948
- RS7378305
- RS7378340
- RS7435196
- RS7442295 – The more common “A” allele is associated with higher blood urate levels and hyperuricemia [18].
- RS7658170
- RS7671266
- RS7672947
- RS7676733
- RS7677710
- RS7680126
- RS7686538
- RS938554
- RS9993410
- 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:
- RS13120400
- 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].
- RS17731538
- RS2199936 – The “A” allele was associated with incident gout [21].
- RS2231137 – The T” (minor) allele was associated with an increased risk of tophaceous gout [22], which causes joint pain and arthritis.
- RS2231142 – The T (minor) allele was associated with an increased risk of gout [23].
- RS2728124
- RS2728125 – The “G” allele was associated with gout [11].
- RS3114018
- RS4148152
- RS4148155
- 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].
- RS12800450 – The “T” allele was associated with reduced blood urate levels [26].
- 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].
- 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].
- 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].
- 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].
- RS12444268 – The “A” allele linked to Type 1 Diabetes [37].
- RS12917707 – The minor “T” allele was associated with a lower risk of chronic kidney disease [38].
- RS13333226 – The minor “G” allele was associated with a lower risk of hypertension [39].
- 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].
