Functional Polymorphisms of the ABCG2 Gene Are Associated with Gout Disease in the Chinese Han Male Population

Abstract

BackgroundGout is a common type of arthritis that is characterized by hyperuricemia, tophi and joint inflammation. Genetic variations in the ABCG2 gene have been reported to influence serum uric acid levels and to participate in the pathogenesis of gout, but no further data have been reported in the Han Chinese population.MethodsPeripheral blood DNA was isolated from 352 male patients with gout and 350 gout-free normal male controls. High-resolution melting analysis and Sanger sequencing were performed to identify the genetic polymorphisms V12M, Q141K and Q126X in the ABCG2 gene. Genotype and haplotype analyses were utilized to determine the disease odds ratios (ORs). A prediction model for gout risk using ABCG2 protein function was established based on the genotype combination of Q126X and Q141K.ResultsFor Q141K, the A allele frequency was 49.6% in the gout patients and 30.9% in the controls (OR 2.20, 95% confidence interval (CI): 1.77–2.74, p = 8.99 × 10−13). Regarding Q126X, the T allele frequency was 4.7% in the gout patients and 1.7% in the controls (OR 2.91, 95% CI: 1.49–5.68, p = 1.57 × 10−3). The A allele frequency for V12M was lower (18.3%) in the gout patients than in the controls (29%) (OR 0.55, 95% CI 0.43–0.71, p = 2.55 × 10−6). In the order of V12M, Q126X and Q141K, the GCA and GTC haplotypes indicated increased disease risk (OR = 2.30 and 2.71, respectively). Patients with mild to severe ABCG2 dysfunction accounted for 78.4% of gout cases.ConclusionThe ABCG2 126X and 141K alleles are associated with an increased risk of gout, whereas 12M has a protective effect on gout susceptibility in the Han Chinese population. ABCG2 dysfunction can be used to evaluate gout risk.

TT genotype of rs2941484 in the human HNF4G gene is associated with hyperuricemia in Chinese Han men

“…The results of our study was consistent with the GWAS on serum urate concentrations [13], we found that the TT genotype of rs2941484 in HNF4G gene was associated with hyperuricemia only in Chinese male population. Some case-control studies have previously identified gene variants that are associated with gender-specific susceptibility to hyperuricemia [31, 32], they both reported the gender-specific gene for hyperuricemia and gout in men rather than in women [33, 34]. The sex specificity demonstrated in the present study was not clear yet.…”

Polymorphisms of the Multidrug Pump ABCG2: A Systematic Review of Their Effect on Protein Expression, Function, and Drug Pharmacokinetics

“…Many studies have found a strong connection between the Q126X polymorphism and increased risk of developing gout (Matsuo et al, 2009;Zhou et al, 2014;Li et al, 2015), with Matsuo et al (2009) showing a significant odds ratio of 5.97. This study also found the Q126X haplotype was present in up to 13.5% of gout patients in a Japanese population (Matsuo et al, 2009).…”

Association of DNA methyltransferase polymorphisms with susceptibility to primary gouty arthritis

“…In the present study, the concentration of sUA, MO, �R, WBC, �LU, LDL�C, VLDL ��d T� w��� �d����fi�d �� b� ��g��fi����l� ��g��� �� ��� g��� �������� �������d w��� ����� in the healthy control subjects, which indicates that a close ����������� b��w��� �UA l�v�l� ��d g��� �x����. C������ ���d��� have demonstrated that genetic variation of ATP binding cassette subfamily G member 2 (ABCG2), solute carrier family 2 member 9 (SLC2A9), and solute carrier family 22 member 12 (SLC22A12) genes are involved in control of sUA levels, and the SNPs of ABCG2, SLC2A9 and SLC22A12 genes may increase the risk for an individual to develop gout (27)(28)(29). However, only ~10% of patients with hyperuricaemia would eventually develop gout (30) while the remaining 90% patients would not, which prompts investigation of the molecular basis involved in the metabolism and regulation of urate to further reveal the pathogenesis of gout.…”