1. Genetic analysis of ABCG2 gene C421A polymorphism with gout disease in Chinese Han male population
- Author
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Changgui Li, Shiguo Liu, Jing Wang, Binbin Wang, Lin Han, Dongmei Meng, Shiyi Zhou, Yunlong Wang, Zhimin Miao, and Xu Ma
- Subjects
Adult ,Male ,China ,Genotype ,Gout ,Population ,DNA Mutational Analysis ,Mutation, Missense ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,chemistry.chemical_compound ,Asian People ,Gene Frequency ,Polymorphism (computer science) ,Genetics ,medicine ,ATP Binding Cassette Transporter, Subfamily G, Member 2 ,Humans ,Hyperuricemia ,education ,Allele frequency ,Genetics (clinical) ,Alleles ,Aged ,education.field_of_study ,Middle Aged ,medicine.disease ,Neoplasm Proteins ,chemistry ,Uric acid ,ATP-Binding Cassette Transporters - Abstract
Gout is the most frequent inXammatory joint disease in men above 40 years of age (Luk and Simkin 2005). Recently, a genome-wide association study identiWed substantial associations between single nucleotide polymorphism (SNPs), rs2231142, in the ATP-binding cassette, sub-family G (WHITE), member 2 (ABCG2) and uric acid concentration and gout in both white and black individuals and may be a causal candidate variant (Dehghan et al. 2008). To clarify the global relevance of the variant rs2231142 (c. C421A), the association needs to be conWrmed by independent studies in diVerent ethnic groups. The objective of this study is to assess the genetic association of SNP in ABCG2 gene with gout in a Chinese Han male population. A total of 200 gout patients and 235 gout-free control were recruited in this study from Qingdao University. The diagnosis of gout was based on the preliminary criteria which was published by the American College of Rheumatology in 1977 for the classiWcation of gout for use in either clinical settings or population-based epidemiologic studies (Wallace et al. 1977). The rs2231142 and nearby regions were ampliWed by polymerase chain reaction (PCR) (PCR primers were shown on supplementary Table 1) and PCR product was sequenced by ABI 3730XL (Applied Biosystems, Foster City, CA) to perform mutational analysis. The associations between biochemical data and gout are listed in Table 1. There were signiWcant diVerence in rs2231142 genotypic and allelic frequencies between gout cases and controls (shown in Table 2). Compared with controls, there was a higher A/A genotype and A allele frequency of rs2231142 in the gout cases (21.8 vs. 8.4% by genotype; 44.9 vs. 32.3% by allele). And the association to gout reached signiWcance ( 2 = 15.91, P < 0.001, crude OR = 3.02, 95% CI 1.36–4.90 and OR (adjusted by age) = 1.80, 95% CI 1.32–2.45 by dominant mode; 2 = 6.82, P = 0.009, OR = 1.67 95% CI 1.54–2.27 by recessive mode). Compared with C/C genotype carriers, there was higher uric acid level in A allele carriers in the gout cases. However, the diVerence did not reach signiWcance (P = 0.066). Rs2231142, the missense SNP in ABCG2 (Q141 K) was associated with uric acid concentration and gout in both white and black individuals and may be a causal candidate variant also for Chinese Han people. The eVects of the polymorphism on the functions of ABCG2 in vitro have been revealed using transfectants that the individuals with the C/C genotype are presumed to have the highest transporter activity (Imai et al. 2002; Kondo et al. 2004; Mizuarai et al. 2004; Woodward et al. 2009). C421A also aVects the B. Wang and Z. Miao contributed equally to the work.
- Published
- 2009