Long-term Effects of the SLC2A9 G844A and SLC22A12 C246T Variants on Serum Uric Acid Concentrations in Children

Overview

Journal BMC Pediatr

Publisher Biomed Central

Specialty Pediatrics

Date 2018 Sep 8

PMID 30189835

Citations 4

Authors

Hye Ah Lee

Bo Hyun Park

Eun Ae Park

Su Jin Cho

Hae Soon Kim

Hyesook Park

Affiliations

Soon will be listed here.

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.

Citing Articles

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SLC2A9 rs16890979 reduces uric acid absorption by kidney organoids.

Wu S, Li C, Li Y, Liu J, Rong C, Pei H Front Cell Dev Biol. 2024; 11:1268226.

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Cohort profile: the Ewha Birth and Growth Study.

Lee H, Park B, Min J, Choi E, Kim U, Park H Epidemiol Health. 2021; 43:e2021016.

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Effects of Prenatal Growth Status on Subsequent Childhood Renal Function Related to High Blood Pressure.

Park B, Lee J, Kim H, Park E, Cho S, Park H J Korean Med Sci. 2019; 34(25):e174.

PMID: 31243933 PMC: 6597485. DOI: 10.3346/jkms.2019.34.e174.

References

Alper Jr A, Chen W, Yau L, Srinivasan S, Berenson G, Hamm L . Childhood uric acid predicts adult blood pressure: the Bogalusa Heart Study. Hypertension. 2004; 45(1):34-8. DOI: 10.1161/01.HYP.0000150783.79172.bb. View

Parsa A, Brown E, Weir M, Fink J, Shuldiner A, Mitchell B . Genotype-based changes in serum uric acid affect blood pressure. Kidney Int. 2011; 81(5):502-7. PMC: 3640827. DOI: 10.1038/ki.2011.414. View

Franco M, Christofalo D, Sawaya A, Ajzen S, Sesso R . Effects of low birth weight in 8- to 13-year-old children: implications in endothelial function and uric acid levels. Hypertension. 2006; 48(1):45-50. DOI: 10.1161/01.HYP.0000223446.49596.3a. View

Mazzali M, Kanellis J, Han L, Feng L, Chen Q, Kang D . Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure-independent mechanism. Am J Physiol Renal Physiol. 2002; 282(6):F991-7. DOI: 10.1152/ajprenal.00283.2001. View

Hurba O, Mancikova A, Krylov V, Pavlikova M, Pavelka K, Stiburkova 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. PMC: 4182324. DOI: 10.1371/journal.pone.0107902. View

Prado E, Maleta K, Ashorn P, Ashorn U, Vosti S, Sadalaki J . Effects of maternal and child lipid-based nutrient supplements on infant development: a randomized trial in Malawi. Am J Clin Nutr. 2016; 103(3):784-93. DOI: 10.3945/ajcn.115.114579. View

Meng Q, Yue J, Shang M, Shan Q, Qi J, Mao Z . Correlation of GLUT9 Polymorphisms With Gout Risk. Medicine (Baltimore). 2015; 94(44):e1742. PMC: 4915872. DOI: 10.1097/MD.0000000000001742. View

Feig D, Johnson R . The role of uric acid in pediatric hypertension. J Ren Nutr. 2007; 17(1):79-83. PMC: 1847593. DOI: 10.1053/j.jrn.2006.10.013. View

Gabrikova D, Bernasovska J, Sokolova J, Stiburkova B . High frequency of SLC22A12 variants causing renal hypouricemia 1 in the Czech and Slovak Roma population; simple and rapid detection method by allele-specific polymerase chain reaction. Urolithiasis. 2015; 43(5):441-5. DOI: 10.1007/s00240-015-0790-4. View

10.

Lee H, Kim Y, Lee H, Gwak H, Hong Y, Kim H . 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. PMC: 10271828. DOI: 10.1017/S1368980015000518. View

11.

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. DOI: 10.1111/j.1523-1755.2004.00839.x. View

12.

Cho S, Kim S, Chung J, Jee S . Discovery of URAT1 SNPs and association between serum uric acid levels and URAT1. BMJ Open. 2015; 5(11):e009360. PMC: 4663448. DOI: 10.1136/bmjopen-2015-009360. View

13.

Yang B, Mo Z, Wu C, Yang H, Yang X, He Y . A genome-wide association study identifies common variants influencing serum uric acid concentrations in a Chinese population. BMC Med Genomics. 2014; 7:10. PMC: 3923000. DOI: 10.1186/1755-8794-7-10. View

14.

Okada Y, Sim X, Go M, Wu J, Gu D, Takeuchi F . Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations. Nat Genet. 2012; 44(8):904-9. PMC: 4737645. DOI: 10.1038/ng.2352. View

15.

Kolz M, Johnson T, Sanna S, Teumer A, Vitart V, Perola M . Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations. PLoS Genet. 2009; 5(6):e1000504. PMC: 2683940. DOI: 10.1371/journal.pgen.1000504. View

16.

Viazzi F, Antolini L, Giussani M, Brambilla P, Galbiati S, Mastriani S . Serum uric acid and blood pressure in children at cardiovascular risk. Pediatrics. 2013; 132(1):e93-9. DOI: 10.1542/peds.2013-0047. View

17.

Dehghan A, Kottgen A, Yang Q, Hwang S, Kao W, Rivadeneira F . Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study. Lancet. 2008; 372(9654):1953-61. PMC: 2803340. DOI: 10.1016/S0140-6736(08)61343-4. View

18.

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 (Copenh). 1977; 85(1):198-208. DOI: 10.1530/acta.0.0850198. View

19.

Stiburkova B, Pavlikova M, Sokolova J, Kozich V . Metabolic syndrome, alcohol consumption and genetic factors are associated with serum uric acid concentration. PLoS One. 2014; 9(5):e97646. PMC: 4020828. DOI: 10.1371/journal.pone.0097646. View

20.

Saroja Voruganti V, Laston S, Haack K, Mehta N, Cole S, Butte N . 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. PMC: 4381775. DOI: 10.3945/ajcn.114.095364. View