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ABCG2 rs2231142 variant in hyperuricemia is modified by SLC2A9 and SLC22A12 polymorphisms and cardiovascular risk factors in an elderly community-dwelling population.
BMC Med Genet. 2020 03 17; 21(1):54.BM

Abstract

BACKGROUND

The ABCG2 rs2231142 single nucleotide polymorphism (SNP) is one of the most significant genetic variants associated with hyperuricemia (HUA) in Asian populations. However, the risk of ABCG2 rs2231142 variants for HUA could interact with other important HUA risk variants and cardiovascular factors. This study investigated the effects of the combined association among ABCG2 rs2231142 and multiple HUA genetic variants or cardiovascular risk factors on HUA risk and serum uric acid (sUA) levels in an elderly Chinese population.

METHODS

A total of 1206 participants over 65 years old were enrolled in this study. Physical and laboratory examinations were performed for all participants. The ABCG2 rs2231142, SLC2A9 rs3733591, and SLC22A12 rs893006 SNPs were assayed using a standardized protocol. Logistic regression analysis and liner regression were adjusted respectively to account for the association between ABCG2 rs2231142 and other genetic variants, as well as between cardiovascular risk factors and HUA risk and sUA levels.

RESULTS

The prevalence of HUA was 14.71% in the elderly community-dwelling population. The ABCG2 rs2231142 risk T allele was associated with HUA risk (odds ratio (OR) = 1.63, 95% confidence interval (CI): 1.27-2.11; p = 1.65 × 10- 4) and with increased sUA levels (Beta = 0.16, p = 6.75 × 10- 9) in the whole study population. Linear regression analysis showed that the mean sUA level increased linearly with the number of risk alleles of the three candidate genetic variants (Beta = 0.18, p = 1.94 × 10- 12) The joint effect of the ABCG2 rs2231142 T allele and cardiovascular risk factors (obesity, hypertension and dyslipidemia) was also associated with increased HUA risk and sUA levels. Each copy of the risk T allele was significantly associated with enhanced HUA risk in patients with hypertriglyceridemia (OR = 2.52, 95% CI: 1.33-4.60; p = 0.003) compared to controls.

CONCLUSION

Our findings reinforce the importance of the ABCG2 rs2231143 variant as a crucial genetic locus for HUA in Chinese populations and demonstrated the combined effects of multiple genetic risk variants and cardiovascular risk exposures on HUA risk and increased sUA level.

Links

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Authors+Show Affiliations

Liu J
Departments of Geriatric Medicine, Xuanwu Hospital, The Capital Medical University, 45 Changchun Street, Xicheng District, Beijing, 100053, China.
Yang W
Departments of Geriatric Medicine, Xuanwu Hospital, The Capital Medical University, 45 Changchun Street, Xicheng District, Beijing, 100053, China. yangw_79@163.com.
Li Y
Departments of Geriatric Medicine, Xuanwu Hospital, The Capital Medical University, 45 Changchun Street, Xicheng District, Beijing, 100053, China.
Wei Z
Departments of Geriatric Medicine, Xuanwu Hospital, The Capital Medical University, 45 Changchun Street, Xicheng District, Beijing, 100053, China.
Dan X
Departments of Neurology, Xuanwu Hospital, The Capital Medical University, Beijing, China.

MeSH

ATP Binding Cassette Transporter, Subfamily G, Member 2AgedAged, 80 and overAgingCardiovascular DiseasesChinaCohort StudiesEffect Modifier, EpidemiologicEpistasis, GeneticFemaleGenes, ModifierGenetic Predisposition to DiseaseGenome-Wide Association StudyGlucose Transport Proteins, FacilitativeHumansHyperuricemiaIndependent LivingMaleNeoplasm ProteinsOrganic Anion TransportersOrganic Cation Transport ProteinsPolymorphism, Single NucleotideRisk FactorsUric Acid

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32183743

Citation

Liu, Jia, et al. "ABCG2 Rs2231142 Variant in Hyperuricemia Is Modified By SLC2A9 and SLC22A12 Polymorphisms and Cardiovascular Risk Factors in an Elderly Community-dwelling Population." BMC Medical Genetics, vol. 21, no. 1, 2020, p. 54.
Liu J, Yang W, Li Y, et al. ABCG2 rs2231142 variant in hyperuricemia is modified by SLC2A9 and SLC22A12 polymorphisms and cardiovascular risk factors in an elderly community-dwelling population. BMC Med Genet. 2020;21(1):54.
Liu, J., Yang, W., Li, Y., Wei, Z., & Dan, X. (2020). ABCG2 rs2231142 variant in hyperuricemia is modified by SLC2A9 and SLC22A12 polymorphisms and cardiovascular risk factors in an elderly community-dwelling population. BMC Medical Genetics, 21(1), 54. https://doi.org/10.1186/s12881-020-0987-4
Liu J, et al. ABCG2 Rs2231142 Variant in Hyperuricemia Is Modified By SLC2A9 and SLC22A12 Polymorphisms and Cardiovascular Risk Factors in an Elderly Community-dwelling Population. BMC Med Genet. 2020 03 17;21(1):54. PubMed PMID: 32183743.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - ABCG2 rs2231142 variant in hyperuricemia is modified by SLC2A9 and SLC22A12 polymorphisms and cardiovascular risk factors in an elderly community-dwelling population. AU - Liu,Jia, AU - Yang,Wei, AU - Li,Yun, AU - Wei,Zhanyun, AU - Dan,Xiaojuan, Y1 - 2020/03/17/ PY - 2019/04/29/received PY - 2020/02/28/accepted PY - 2020/3/19/entrez PY - 2020/3/19/pubmed PY - 2020/5/6/medline KW - ABCG2 KW - Hypertension KW - Polymorphisms KW - Triglyceridemia KW - Uric acid SP - 54 EP - 54 JF - BMC medical genetics JO - BMC Med Genet VL - 21 IS - 1 N2 - BACKGROUND: The ABCG2 rs2231142 single nucleotide polymorphism (SNP) is one of the most significant genetic variants associated with hyperuricemia (HUA) in Asian populations. However, the risk of ABCG2 rs2231142 variants for HUA could interact with other important HUA risk variants and cardiovascular factors. This study investigated the effects of the combined association among ABCG2 rs2231142 and multiple HUA genetic variants or cardiovascular risk factors on HUA risk and serum uric acid (sUA) levels in an elderly Chinese population. METHODS: A total of 1206 participants over 65 years old were enrolled in this study. Physical and laboratory examinations were performed for all participants. The ABCG2 rs2231142, SLC2A9 rs3733591, and SLC22A12 rs893006 SNPs were assayed using a standardized protocol. Logistic regression analysis and liner regression were adjusted respectively to account for the association between ABCG2 rs2231142 and other genetic variants, as well as between cardiovascular risk factors and HUA risk and sUA levels. RESULTS: The prevalence of HUA was 14.71% in the elderly community-dwelling population. The ABCG2 rs2231142 risk T allele was associated with HUA risk (odds ratio (OR) = 1.63, 95% confidence interval (CI): 1.27-2.11; p = 1.65 × 10- 4) and with increased sUA levels (Beta = 0.16, p = 6.75 × 10- 9) in the whole study population. Linear regression analysis showed that the mean sUA level increased linearly with the number of risk alleles of the three candidate genetic variants (Beta = 0.18, p = 1.94 × 10- 12) The joint effect of the ABCG2 rs2231142 T allele and cardiovascular risk factors (obesity, hypertension and dyslipidemia) was also associated with increased HUA risk and sUA levels. Each copy of the risk T allele was significantly associated with enhanced HUA risk in patients with hypertriglyceridemia (OR = 2.52, 95% CI: 1.33-4.60; p = 0.003) compared to controls. CONCLUSION: Our findings reinforce the importance of the ABCG2 rs2231143 variant as a crucial genetic locus for HUA in Chinese populations and demonstrated the combined effects of multiple genetic risk variants and cardiovascular risk exposures on HUA risk and increased sUA level. SN - 1471-2350 UR - https://www.unboundmedicine.com/medline/citation/32183743/ABCG2_rs2231142_variant_in_hyperuricemia_is_modified_by_SLC2A9_and_SLC22A12_polymorphisms_and_cardiovascular_risk_factors_in_an_elderly_community_dwelling_population_ DB - PRIME DP - Unbound Medicine ER -