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Published in: BMC Pediatrics 1/2018

Open Access 01-12-2018 | Research article

Long-term effects of the SLC2A9 G844A and SLC22A12 C246T variants on serum uric acid concentrations in children

Authors: Hye Ah Lee, Bo Hyun Park, Eun Ae Park, Su Jin Cho, Hae Soon Kim, Hyesook Park

Published in: BMC Pediatrics | Issue 1/2018

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Abstract

Background

We evaluated the effects of two single-nucleotide polymorphisms on UA concentrations in the first decade of life using repeated-measures data.

Methods

We included all subjects who were followed-up at least once and for whom we had both UA and genotypic data (i.e., 375, 204, 307, and 363 patients aged 3, 5, 7, and 9 years, respectively). All participated in the Ewha Birth and Growth Cohort study. We used a mixed model analysis to estimate the longitudinal association of serum UA concentration due to the rs3825017 (SLC22A12 c. 246C > T) and rs16890979 (SLC2A9 c. 844G > A) genotypes.

Results

Overall, the tracking coefficient of UA concentrations in children 3 to 9 years of age was 0.31, and was higher in boys than in girls (0.34 vs. 0.29, respectively). Regarding individual variance, serum UA concentrations decreased as age increased (β = − 0.07, p < 0.05), but there were no significant differences by sex. The effects of rs3825017 on UA concentration were significant in boys, but not in girls. Boys with the T allele of rs3825017 had higher concentrations than their counterparts regardless of the time of follow-up. The rs16890979 genotypes were not significantly associated with serum UA concentration in either sex.

Conclusion

This study showed that rs3825017 in the SLC22A12 gene was associated with UA concentration in childhood.
Literature
1.
go back to reference Kutzing MK, Firestein BL. Altered uric acid levels and disease states. J Pharmacol Exp Ther. 2008;324(1):1–7.CrossRefPubMed Kutzing MK, Firestein BL. Altered uric acid levels and disease states. J Pharmacol Exp Ther. 2008;324(1):1–7.CrossRefPubMed
2.
go back to reference Kolz M, Johnson T, Sanna S, Teumer A, Vitart V, Perola M, et al. Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations. PLoS Genet. 2009;5(6):e1000504.CrossRefPubMedPubMedCentral Kolz M, Johnson T, Sanna S, Teumer A, Vitart V, Perola M, et al. Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations. PLoS Genet. 2009;5(6):e1000504.CrossRefPubMedPubMedCentral
4.
go back to reference Alper AB Jr, Chen W, Yau L, Srinivasan SR, Berenson GS, Hamm LL. Childhood uric acid predicts adult blood pressure: the Bogalusa heart study. Hypertension. 2005;45(1):34–8.CrossRefPubMed Alper AB Jr, Chen W, Yau L, Srinivasan SR, Berenson GS, Hamm LL. Childhood uric acid predicts adult blood pressure: the Bogalusa heart study. Hypertension. 2005;45(1):34–8.CrossRefPubMed
5.
go back to reference Dehghan A, Köttgen A, Yang Q, Hwang SJ, Kao WL, Rivadeneira F, et al. Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study. Lancet. 2008;372(9654):1953–61.CrossRefPubMedPubMedCentral Dehghan A, Köttgen A, Yang Q, Hwang SJ, Kao WL, Rivadeneira F, et al. Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study. Lancet. 2008;372(9654):1953–61.CrossRefPubMedPubMedCentral
6.
go back to reference Whitfield JB, Martin NG. Inheritance and alcohol as factors influencing plasma uric acid levels. Acta Genet Med Gemellol. 1983;32:117–26.CrossRefPubMed Whitfield JB, Martin NG. Inheritance and alcohol as factors influencing plasma uric acid levels. Acta Genet Med Gemellol. 1983;32:117–26.CrossRefPubMed
7.
go back to reference Claverie-Martin F, Trujillo-Suarez J, Gonzalez-Acosta H, Aparicio C, Justa Roldan ML, Stiburkova B, Ichida K, Martín-Gomez MA, Herrero Goñi M, Carrasco Hidalgo-Barquero M, Iñigo V, Enriquez R, Cordoba-Lanus E, Garcia-Nieto VM, RenalTube Group. URAT1 and GLUT9 mutations in Spanish patients with renal hypouricemia. Clin Chim Acta. 2018;481:83–9. https://doi.org/10.1016/j.cca.2018.02.030.CrossRefPubMed Claverie-Martin F, Trujillo-Suarez J, Gonzalez-Acosta H, Aparicio C, Justa Roldan ML, Stiburkova B, Ichida K, Martín-Gomez MA, Herrero Goñi M, Carrasco Hidalgo-Barquero M, Iñigo V, Enriquez R, Cordoba-Lanus E, Garcia-Nieto VM, RenalTube Group. URAT1 and GLUT9 mutations in Spanish patients with renal hypouricemia. Clin Chim Acta. 2018;481:83–9. https://​doi.​org/​10.​1016/​j.​cca.​2018.​02.​030.CrossRefPubMed
9.
go back to reference Chen Y, Ying Y, Shi S, Li L, Huang Y, Ye H, Gong O, Huang H, Ji H, Huang T, Duan S. A systematic review and meta-analysis of 4 candidate polymorphisms with the risk of gout. Int J Clin Exp Med. 2016;9(8):16025–33. Chen Y, Ying Y, Shi S, Li L, Huang Y, Ye H, Gong O, Huang H, Ji H, Huang T, Duan S. A systematic review and meta-analysis of 4 candidate polymorphisms with the risk of gout. Int J Clin Exp Med. 2016;9(8):16025–33.
10.
go back to reference Stiburkova B, Pavelcova K, Zavada J, Petru L, Simek P, Cepek P, Pavlikova M, Matsuo H, Merriman TR, Pavelka K. Functional non-synonymous variants of ABCG2 and gout risk. Rheumatology (Oxford). 2017;56(11):1982–92.CrossRef Stiburkova B, Pavelcova K, Zavada J, Petru L, Simek P, Cepek P, Pavlikova M, Matsuo H, Merriman TR, Pavelka K. Functional non-synonymous variants of ABCG2 and gout risk. Rheumatology (Oxford). 2017;56(11):1982–92.CrossRef
11.
go back to reference Higashino T, Takada T, Nakaoka H, Toyoda Y, Stiburkova B, Miyata H, et al. Multiple common and rare variants of ABCG2 cause gout. RMD Open. 2017;3(2):e000464.CrossRefPubMedPubMedCentral Higashino T, Takada T, Nakaoka H, Toyoda Y, Stiburkova B, Miyata H, et al. Multiple common and rare variants of ABCG2 cause gout. RMD Open. 2017;3(2):e000464.CrossRefPubMedPubMedCentral
12.
go back to reference Iwai N, Mino Y, Hosoyamada M, Tago N, Kokubo Y, Endou H. A high prevalence of renal hypouricemia caused by inactive SLC22A12 in Japanese. Kidney Int. 2004;66(3):935–44.CrossRefPubMed Iwai N, Mino Y, Hosoyamada M, Tago N, Kokubo Y, Endou H. A high prevalence of renal hypouricemia caused by inactive SLC22A12 in Japanese. Kidney Int. 2004;66(3):935–44.CrossRefPubMed
15.
16.
go back to reference Franco MC, Christofalo DM, Sawaya AL, Ajzen SA, Sesso R. Effects of low birth weight in 8- to 13-year-old children: implications in endothelial function and uric acidlevels. Hypertension. 2006;48(1):45–50.CrossRefPubMed Franco MC, Christofalo DM, Sawaya AL, Ajzen SA, Sesso R. Effects of low birth weight in 8- to 13-year-old children: implications in endothelial function and uric acidlevels. Hypertension. 2006;48(1):45–50.CrossRefPubMed
17.
go back to reference Lin WT, Huang HL, Huang MC, Chan TF, Ciou SY, Lee CY, et al. Effects on uric acid, body mass index and blood pressure in adolescents of consuming beverages sweetened with high-fructose corn syrup. Int J Obes (Lond). 2013;37(4):532–9.CrossRef Lin WT, Huang HL, Huang MC, Chan TF, Ciou SY, Lee CY, et al. Effects on uric acid, body mass index and blood pressure in adolescents of consuming beverages sweetened with high-fructose corn syrup. Int J Obes (Lond). 2013;37(4):532–9.CrossRef
18.
go back to reference Viazzi F, Antolini L, Giussani M, Brambilla P, Galbiati S, Mastriani S, et al. Serum uric acid and blood pressure in children at cardiovascular risk. Pediatrics. 2013;132(1):e93–9.CrossRefPubMed Viazzi F, Antolini L, Giussani M, Brambilla P, Galbiati S, Mastriani S, et al. Serum uric acid and blood pressure in children at cardiovascular risk. Pediatrics. 2013;132(1):e93–9.CrossRefPubMed
19.
go back to reference Voruganti VS, Laston S, Haack K, Mehta NR, Cole SA, Butte NF, et al. Serum uric acid concentrations and SLC2A9 genetic variation in Hispanic children: the viva La Familia study. Am J Clin Nutr. 2015;101(4):725–32.CrossRefPubMedPubMedCentral Voruganti VS, Laston S, Haack K, Mehta NR, Cole SA, Butte NF, et al. Serum uric acid concentrations and SLC2A9 genetic variation in Hispanic children: the viva La Familia study. Am J Clin Nutr. 2015;101(4):725–32.CrossRefPubMedPubMedCentral
20.
go back to reference Lee HA, Park EA, Cho SJ, Kim HS, Kim YJ, Lee H, et al. Mendelian randomization analysis of the effect of maternal homocysteine during pregnancy, as represented by maternal MTHFR C677T genotype, on birth weight. J Epidemiol. 2013;23(5):371–5.CrossRefPubMedPubMedCentral Lee HA, Park EA, Cho SJ, Kim HS, Kim YJ, Lee H, et al. Mendelian randomization analysis of the effect of maternal homocysteine during pregnancy, as represented by maternal MTHFR C677T genotype, on birth weight. J Epidemiol. 2013;23(5):371–5.CrossRefPubMedPubMedCentral
21.
go back to reference Lee HA, Kim YJ, Lee H, Gwak HS, Hong YS, Kim Q, et al. The preventive effect of breast-feeding for longer than 6 months on early pubertal development among children aged 7-9 years in Korea. Public Health Nutr. 2015;18(18):3300–7.CrossRefPubMed Lee HA, Kim YJ, Lee H, Gwak HS, Hong YS, Kim Q, et al. The preventive effect of breast-feeding for longer than 6 months on early pubertal development among children aged 7-9 years in Korea. Public Health Nutr. 2015;18(18):3300–7.CrossRefPubMed
22.
go back to reference Twisk JWR. Applied longitudinal data analysis for epidemiology: a practical guide. Cambridge: Cambridge University Press; 2003. p. 225–7. Twisk JWR. Applied longitudinal data analysis for epidemiology: a practical guide. Cambridge: Cambridge University Press; 2003. p. 225–7.
23.
go back to reference Pearson N, Salmon J, Campbell K, Crawford D, Timperio A. Tracking of children's body-mass index, television viewing and dietary intake over five-years. Prev Med. 2011;53(4–5):268–70.CrossRefPubMed Pearson N, Salmon J, Campbell K, Crawford D, Timperio A. Tracking of children's body-mass index, television viewing and dietary intake over five-years. Prev Med. 2011;53(4–5):268–70.CrossRefPubMed
24.
go back to reference Prado EL, Maleta K, Ashorn P, Ashorn U, Vosti SA, Sadalaki J, Dewey KG. Effects of maternal and child lipid-based nutrient supplements on infant development: a randomized trial in Malawi. Am J Clin Nutr. 2016;103:784–93.CrossRefPubMed Prado EL, Maleta K, Ashorn P, Ashorn U, Vosti SA, Sadalaki J, Dewey KG. Effects of maternal and child lipid-based nutrient supplements on infant development: a randomized trial in Malawi. Am J Clin Nutr. 2016;103:784–93.CrossRefPubMed
25.
go back to reference Okada Y, Sim X, Go MJ, Wu JY, Gu D, Takeuchi F, et al. Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations. Nat Genet. 2012;44(8):904–9.CrossRefPubMedPubMedCentral Okada Y, Sim X, Go MJ, Wu JY, Gu D, Takeuchi F, et al. Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations. Nat Genet. 2012;44(8):904–9.CrossRefPubMedPubMedCentral
26.
go back to reference Parsa A, Brown E, Weir MR, Fink JC, Shuldiner AR, Mitchell BD, et al. Genotype-based changes in serum uric acid affect blood pressure. Kidney Int. 2012;81(5):502–7.CrossRefPubMed Parsa A, Brown E, Weir MR, Fink JC, Shuldiner AR, Mitchell BD, et al. Genotype-based changes in serum uric acid affect blood pressure. Kidney Int. 2012;81(5):502–7.CrossRefPubMed
28.
go back to reference Meng Q, Yue J, Shang M, Shan Q, Qi J, Mao Z, et al. Correlation of GLUT9 polymorphisms with gout risk. Medicine (Baltimore). 2015;94(44):e1742.CrossRef Meng Q, Yue J, Shang M, Shan Q, Qi J, Mao Z, et al. Correlation of GLUT9 polymorphisms with gout risk. Medicine (Baltimore). 2015;94(44):e1742.CrossRef
29.
go back to reference Yang B, Mo Z, Wu C, Yang H, Yang X, He Y, et al. A genome-wide association study identifies common variants influencing serum uric acid concentrations in a Chinese population. BMC Med Genomics. 2014;7:10.CrossRefPubMedPubMedCentral Yang B, Mo Z, Wu C, Yang H, Yang X, He Y, et al. A genome-wide association study identifies common variants influencing serum uric acid concentrations in a Chinese population. BMC Med Genomics. 2014;7:10.CrossRefPubMedPubMedCentral
30.
go back to reference Hurba O, Mancikova A, Krylov V, Pavlikova M, Pavelka K, Stibůrková B. Complex analysis of urate transporters SLC2A9, SLC22A12 and functional characterization of non-synonymous allelic variants of GLUT9 in the Czech population: no evidence of effect on hyperuricemia and gout. PLoS One. 2014;9(9):e107902.CrossRefPubMedPubMedCentral Hurba O, Mancikova A, Krylov V, Pavlikova M, Pavelka K, Stibůrková B. Complex analysis of urate transporters SLC2A9, SLC22A12 and functional characterization of non-synonymous allelic variants of GLUT9 in the Czech population: no evidence of effect on hyperuricemia and gout. PLoS One. 2014;9(9):e107902.CrossRefPubMedPubMedCentral
31.
go back to reference Li C, Han L, Levin AM, Song H, Yan S, Wang Y, et al. Multiple single nucleotide polymorphisms in the human urate transporter 1 (hURAT1) gene are associated with hyperuricaemia in Han Chinese. J Med Genet. 2010;47(3):204–10.CrossRefPubMed Li C, Han L, Levin AM, Song H, Yan S, Wang Y, et al. Multiple single nucleotide polymorphisms in the human urate transporter 1 (hURAT1) gene are associated with hyperuricaemia in Han Chinese. J Med Genet. 2010;47(3):204–10.CrossRefPubMed
32.
go back to reference McArdle PF, Parsa A, Chang YC, Weir MR, O'Connell JR, Mitchell BD, et al. A common non-synonymous variant in GLUT9 is a determinant of serum uric acid levels in old order Amish. Arthritis Rheum. 2008;58(9):2874–81.CrossRefPubMedPubMedCentral McArdle PF, Parsa A, Chang YC, Weir MR, O'Connell JR, Mitchell BD, et al. A common non-synonymous variant in GLUT9 is a determinant of serum uric acid levels in old order Amish. Arthritis Rheum. 2008;58(9):2874–81.CrossRefPubMedPubMedCentral
33.
go back to reference Adamopoulos D, Vlassopoulos C, Seitanides B, Contoyiannis P, Vassilopoulos P. The relationship of sex steroids to uric acid levels in plasma and urine. Acta Endocrinol. 1977;85(1):198–208.PubMedCrossRef Adamopoulos D, Vlassopoulos C, Seitanides B, Contoyiannis P, Vassilopoulos P. The relationship of sex steroids to uric acid levels in plasma and urine. Acta Endocrinol. 1977;85(1):198–208.PubMedCrossRef
34.
go back to reference Mazzali M, Kanellis J, Han L, Feng L, Xia Y-Y, Chen Q, et al. Hyperuricemia induces a primary arteriolpathy in rats by a blood pressure-independent mechanism. Am J Physiol Renal Physiol. 2002;6:F991–7.CrossRef Mazzali M, Kanellis J, Han L, Feng L, Xia Y-Y, Chen Q, et al. Hyperuricemia induces a primary arteriolpathy in rats by a blood pressure-independent mechanism. Am J Physiol Renal Physiol. 2002;6:F991–7.CrossRef
35.
go back to reference Sánchez-Lozada LG, Tapia E, Avila-Casado C, Soto V, Franco M, Santamaría J, et al. Mild hyperuricemia induces glomerular hypertension in normal rats. Am J Physiol Renal Physiol. 2002;283(5):F1105–10.CrossRefPubMed Sánchez-Lozada LG, Tapia E, Avila-Casado C, Soto V, Franco M, Santamaría J, et al. Mild hyperuricemia induces glomerular hypertension in normal rats. Am J Physiol Renal Physiol. 2002;283(5):F1105–10.CrossRefPubMed
36.
go back to reference Watanabe S, Kang DH, Feng L, Nakagawa T, Kanellis J, Lan H, et al. Uric acid, hominoid evolution, and the pathogenesis of salt-sensitivity. Hypertension. 2002;40(3):355–60.CrossRefPubMed Watanabe S, Kang DH, Feng L, Nakagawa T, Kanellis J, Lan H, et al. Uric acid, hominoid evolution, and the pathogenesis of salt-sensitivity. Hypertension. 2002;40(3):355–60.CrossRefPubMed
Metadata
Title
Long-term effects of the SLC2A9 G844A and SLC22A12 C246T variants on serum uric acid concentrations in children
Authors
Hye Ah Lee
Bo Hyun Park
Eun Ae Park
Su Jin Cho
Hae Soon Kim
Hyesook Park
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Pediatrics / Issue 1/2018
Electronic ISSN: 1471-2431
DOI
https://doi.org/10.1186/s12887-018-1272-y

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