ABCMdb

PMID: 22945592

Reginato AM, Mount DB, Yang I, Choi HK
The genetics of hyperuricaemia and gout.
Nat Rev Rheumatol. 2012 Oct;8(10):610-21. doi: 10.1038/nrrheum.2012.144. Epub 2012 Sep 4., [PubMed]

Sentences

No. Mutations Sentence Comment

36 ABCG2 p.Gln141Lys ABCG2 p.Gln141Lys ABCG2 p.Gln141Lys ABCG2 p.Gln141Lys An analysis of the Atherosclerosis Risk in Com-muni- ties study showed that at least 10% of all gout cases in white individuals were attributable to the Gln141Lys causal variant.62 However, the frequency of the Gln141Lys risk allele has been reported to be as high as 32% in the Asian population.32,60 Although both Maoris and Pacific Islanders are known to have an increased risk of gout, the Gln141Lys variant is strongly associated with gout only in the western Polynesian population.61 This distribu-tion might be the result of chance depletion of the allele dur-ing eastward migration, as the frequency of the Gln141Lys variant in white populations has been reported to be <12%.37,61 SLC22A12 The SLC22A12 gene encodes URAT1, an essential urate transporter in proximal tubules that has a role in the apical absorption of urate66 and is a target of both urico-suric and antiuricosuric agents (Figure 2). Login to comment 58 ABCG2 p.Gln141Lys ABCG2 p.Gln126* In the liver, GCKR regulates glucokinase75,85 by mediating the phosphorylation of glucose to glucose‑6-phosphate, a precursor of liver glycogen synthesis and of de novo purine synthesis.75,85 A deficiency in the activity of glucose‑6-phosphatase causes glycogen storage disease type 1 (also known as von Gierke disease), which is characterized by hypertriglyceridaemia and hyperuricaemia.75,85 The GCKR SNP rs780094 might affect both serum uric acid and triglyceride levels (which are associated with insulin resistance) via a common mediator.75 Interestingly, GCKR is associated with insulin resistance,32 glucose level, triglyceride level, and C‑reactive protein,86 which are components of metabolic syndrome.75 Table 2 | SLC2A9, ABCG2 and SLC22A12 variants associated with serum uric acid levels, FeUA and gout Variant Location Phenotype Populations SLC2A9 (chromosome 4) rs1014290 Intron 3 SUA, FeUA, gout European ancestry34 rs6449213 Intron 4 SUA, FeUA, gout White,34-37,43 African American51,72 rs16890979 Exon 6 SUA, gout White,37,42,44 African American,72 Amish55 rs734553 Intron 6 SUA, gout White,32,39,44 Icelandic,13 African American72 rs7442295 Intron 6 SUA, gout White 35,38,39,44 rs737267 Intron 7 SUA, FeUA, gout European ancestry34,44 rs6855911 Intron 7 SUA, gout White,35,38,39,44 African American72 rs13129697 Intron 7 SUA, gout White,33,44 African American72 rs2241480 Intron 8 SUA, gout European ancestry72 rs7663032 Intron 9 SUA, gout African American,72 Croatian44 rs3775948 Intron 9 SUA Croatian,44 African American51 rs16890979 Intergenic SUA, gout White,37 Amish,55 Croatian,44 Pacific Islander,42 New Zealander42 rs717615 Intergenic SUA Croatian44 rs6856396 Intergenic SUA African American51 rs10489070 Intergenic Gout Amish55 ABCG2 (chromosome 4) rs2231137 Exon 2 SUA Japanese63 rs72552713 (Q126X) Exon 4 SUA, gout Japanese63 rs2231142 (Q141K) Exon 5 FeUA, SUA, gout White,32,37,39,44,62 African,37,72 Chinese,60 Icelandic,13 Japanese,59,63 Pacific Islander,61 New Zealander31,61 rs2199936 Intergenic SUA White 32,33,44 SLC22A12 (chromosome 11) rs11231825 Exon 1 FeUA, SUA Chinese,70 White,32,68 African American72 rs3825016 Exon 2 FeUA German68 rs12800450 Exon 2 SUA African American72 rs161109885 Intron 3 SUA Chinese73 rs893006 Intron 4 SUA Japanese,67 Chinese71 rs1529909 Intron 4 FeUA, SUA Korean74 rs475688 Intron 4 Gout Chinese,70 Solomon Islander70 rs17300741 Intron 4 SUA European32,75 rs7932775 Exon 8 SUA, FeUA, gout German,68 Chinese,70,73 Solomon Islander70 rs505802 Intergenic SUA European,32,44 African American72 rs11602903 Intergenic FeUA, SUA German,68 Chinese73 Abbreviations: FeUA, fractional excretion of urate; SUA, serum uric acid. Login to comment