ABCG2 rs2231142 variant in hyperuricemia is modified by SLC2A9 and SLC22A12 polymorphisms and cardiovascular risk factors in an elderly community-dwelling population

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.

Polymorphisms of the genes ABCG2, SLC22A12 and XDH and their relation with hyperuricemia and hypercholesterolemia in Mexican young adults

“…We found that the minor allele frequency was 0.37 for the C allele, contrary to what was reported in a Chinese population, where the C allele had a higher frequency, in addition to its being associated with hypertension (Wu et al, 2015). However, the link between the XDH (rs1042039) polymorphism and hypertension was not demostrated in Taiwanese women (Lee et al, 2019). In the present study, we did not find a statistically significant different distribution of the C allele between the hyperuricemic and normouricemic groups, and the risk allele was also not associated with any component of the metabolic syndrome.…”

“…between serum uric acid levels and the traits of metabolic syndrome has been previously analyzed (Lin et al, 2006;Zhang et al, 2020a), although some authors found no causal evidence of uric acid levels being associated with metabolic syndrome and its components (Wang et al, 2020). According to our results, being a man, being overweight or obese, or having dyslipidemia are related to high uric acid levels (Figure 1).…”

“…Likewise, the involvement of uric acid in lipid metabolism can lead to hyperuricemia, a condition considered as predictor factor of dyslipidemia (Kuwabara et al 2020;Lima et al, 2015;Son et al, 2016) and can subsequently alter blood pressure (Teng et al, 2011;Zhang et al, 2020a). In this way, our results summarized in Figure 1 show that being male, being obese and having dyslipidemia increases the risk of hyperuricemia (Liu et al, 2020a).…”

“…Finally, hyperuricemia is an undesirable condition that has been seen as a minor trait of metabolic syndrome, cardiovascular risk, as well as other types of disorders such as psoriasis and alopecia, which have been associated with high levels of blood uric acid (Guo et al, 2020;Ma et al, 2020;Talebi et al, 2020;Zhang et al, 2020a). Even though our criterion for hyperuricemia were defined as blood uric acid >6 mg/dL for women and 7 mg/dL for men, cut-off points could be reconsidered according to the considerations made by Alegría-Díaz et al (2018).…”

A pharmacogenetics study of platinum-based chemotherapy in lung cancer: ABCG2 polymorphism and its genetic interaction with SLC31A1 are associated with response and survival

“…In a genome-wide association study, additive genetic risk score of nonsynonymous variants of ABCG2 (rs2231142) and SLC2A9 (rs16890979) showed graded associations with uric acid and gout 56 . It was also recently reported that the association of ABCG2 rs2231142 with hyperuricemia is modified by SLC2A9 polymorphism in an elderly Chinese population 57 . Although the causative mechanism for the synergistic effects of polymorphisms in platinum intake and export pathways, such as SLC31A1 and ABCG2 , is still largely unknown, the association of their interaction with clinical outcomes suggests the combined relevant genotypes of SLC31A1 and ABCG2 as potential pertinent and actionable pharmacogenetic biomarkers for platinum-based chemotherapy of NSCLC, especially for some demographically stratified subgroups patients.…”