Table 1.
Overview of targeted single nucleotide polymorphisms (SNPs).
| Gene (Protein) | Protein Function | SNP * | SNP Effect | References |
|---|---|---|---|---|
|
ABCG2 (ABCG2) |
Major urate efflux transporter expressed in the kidney, liver, and gastrointestinal tract. | rs2231142 (G > T) | Missense variant resulting in Q141K (Glu141Lys) amino acid substitution leading to a reduction in ABCG2-mediated urate transport, urate under-excretion, hyperuricemia, and gout. | [23,24,25] |
|
SLC2A9 (GLUT9) |
High-capacity urate, fructose, and glucose transporter expressed in liver, kidney, chondrocytes tissues shown to be strongly associated with hyperuricemia and gout. | rs734553 (G > T) |
Intronic variant associated with increased susceptibility to gout due to altered transporter affinity for urate. | [23,26] |
|
SLC16A9 (MCT9) |
Monocarboxylic acid transporter protein across cell membranes. | rs1171614 (C > T) |
5′ untranslated region (UTR) variant associated with lower serum urate concentrations in individuals of European ancestry. | [14,23] |
|
SLC17A1 (NPT1) |
Uric acid transport protein localized at the apical membrane of the renal proximal tubule. | rs1183201 (T > A) |
Intronic variant reported being in high linkage disequilibrium (r2 = 0.97) with rs1165205, an intronic SNP in SLC17A3 found to be associated with SU levels and gout risk factors. | [21,23] |
|
SLC22A11 (OAT4) |
An organic anion-dicarboxylate exchanger mediates transport across the apical membrane of the kidney. | rs2078267 (C > T) |
Noncoding transcript exon variant associated with lower SU levels in individuals of European ancestry. | [23] |
|
SLC22A12 (URAT1) |
Major urate transporter that mediates the non-voltage dependent exchange of urate for several organic anions, localized at the apical membrane of the renal proximal tubule | rs505802 (C > T) |
Intergenic variant associated with lower serum urate concentrations in individuals of European ancestry. | [23] |
|
GCKR (GCKR) |
Glucokinase regulator associated with metabolic traits such as insulin resistance that may be linked to urate concentrations | rs1260326 (C > T) |
Missense variant that causes a Leu446Pro amino acid substitution within the glucokinase regulatory protein gene. Associated with lower fasting glucose levels and higher risk for elevated triglyceride levels, SU, and gout (OR = 1.39, 95%CI 1.23;1.57). | [23,24,25] |
|
INHBC (INHBC) |
Member of the transforming growth factor ß superfamily that may inhibit activin A signaling, affecting a variety of biologic functions including pituitary hormone secretion and insulin secretion. | rs3741414 (C > T) |
3′ untranslated region (UTR) variant was reported to interact with OAT4, URAT1, and NTP1 via their C-terminal PDZ motifs and was found to have an association with SU levels. | [24,27] |
|
RREB1 (RREB1) |
Zinc finger transcription factor that binds to gene promoters and regulates calcitonin gene and androgen receptor. | rs675209 (C > T) |
Intergenic variant associated with a higher risk for gout in individuals of European ancestry. | [24,27] |
|
PDZK1 (PDZ) |
Scaffolding protein forms a bidirectional urate transport system to maintain balanced urate levels at the apical membrane of renal proximal tubules. | rs12129861 (C > T) |
Intergenic variant inked with lower serum urate concentrations in individuals of European ancestry. | [23,28] |
|
NRXN2 (Neurexin 2) |
Member of the neurexin gene family that serves as a cell adhesion molecule. | rs478607 (G > A) |
Missense variant associated with higher serum urate concentrations in individuals of Chinese descent. | [24] |
* Bolded letter allele indicates the risk allele, which is defined as the allele that is associated with baseline or higher risk for HU or gout.