J Korean Med Sci.  2017 Sep;32(9):1451-1459. 10.3346/jkms.2017.32.9.1451.

ABCG2 Polymorphism Is Associated with Hyperuricemia in a Study of a Community-Based Korean Cohort

• Son CN
• Bang SY
• Kim SH
• Sung YK
• Bae SC
• Jun JB

• KMID: 2385951
• DOI: http://doi.org/10.3346/jkms.2017.32.9.1451

Abstract

The purpose of the present study was to find novel loci associated with hyperuricemia using data from a genome-wide association study (GWAS) conducted on healthy Koreans. We conducted a GWAS using data from a community-based cohort study where 3,647 subjects aged 40-89 were recruited by the Korea National Institute of Health (KNIH). The community-based cohort consisted of subjects who did not suffer from any of 6 major diseases (hypertension, hyperlipidemia, diabetes, heart diseases, brain diseases, and cancers). Epidemiologic information includes 249 traits such as epidemiological surveys, physical examinations, and laboratory tests. A total of 3,647 participants, including 234 hyperuricemia cases (serum uric acid [SUA] level was 7 mg/dL or higher) and 3,413 controls, were genotyped by Illumina HumanOmni1-Quad BeadChip GWAS array at KNIH. In the multivariate regression analysis of clinical variables, significant variables associated with hyperuricemia were male gender (odds ratio [OR], 5.526; P = 3.2 × 10⁻¹â°), old age (OR, 1.017; P = 0.040), high body mass index (BMI) (OR, 1.147; P = 5.4 × 10⁻⁷), current alcohol intake (OR, 2.413; P = 4.7 × 10⁻⁷), and high creatinine (OR, 1.647; P = 1.6 × 10⁻¹³). We identified a hyperuricemia susceptible loci (rs2054576 in ABCG2, OR, 1.883; P = 4.7 × 10⁻⁸) that passed a genome-wide significance threshold, adjusted by clinical variables (male, age, BMI, current alcohol, and creatinine). It was first identified that rs2054576 in ABCG2 is associated with hyperuricemia. Our results should be validated through replication studies among other Korean subjects or various ethnic groups.

Keyword

ABCG2; Hyperuricemia; Uric Acid

MeSH Terms

Body Mass Index
Brain Diseases
Cohort Studies*
Creatinine
Ethnic Groups
Genome-Wide Association Study
Heart Diseases
Humans
Hyperlipidemias
Hyperuricemia*
Korea
Male
Physical Examination
Uric Acid
Creatinine
Uric Acid

Figure

• 

  Fig. 1 Flowchart illustrating inclusion and exclusion criteria for the study subjects. SUA = serum uric acid, CAVAS = cardio vascular disease association study, KoGES = Korean genome and epidemiology study. *The subjects were selected from CAVAS of the KoGES Project from 2004 to 2008; †Hyperuricemia was defined as SUA level ≥ 7 mg/dL (12).

• 

  Fig. 2 QQ plot showing the expected and observed distributions of log10 (P) values in hyperuricemia. An obvious deviation from the expectation (straight red line) represents the presence of true-positive association signals. QQ = quantile-quantile.

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  Fig. 3 Manhattan plots of the genome-wide association signals with hyperuricemia. The strength of association (−log10 [P] values) on y-axis was plotted against the chromosomal base-pair positions on the x-axis. The red line indicates the genome wide significance threshold (5 × 10−8), while the blue line indicates a threshold of 10−5.

• 

  Fig. 4 Regional association plots at the most significant loci associated with hyperuricemia. The plots of genetic loci on chromosome 4 are shown as they were created using LocusZoom. Each point represents a SNP plotted with their −log10 (P) values as a function of genomic position (NCBI Build 36). The lead SNP (rs2054576) is represented by purple diamond. The color coding of all other SNPs (circles) indicates LD with rs2054576 (red r2 ≥ 0.8, gold 0.6 ≤ r2 < 0.8, green 0.4 ≤ r2 < 0.6, cyan 0.2 ≤ r2 < 0.4, blue r2 < 0.2, grey r2 unknown). SNP = single nucleotide polymorphism, NCBI = National Center for Biotechnology Information, LD = linkage disequilibrium.

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  Fig. 5 Linkage disequilibrium as measured by r2 in ABCG2, based on SNPinfo. SNP = single nucleotide polymorphism, LD = linkage disequilibrium, MAF = minor allele frequency.

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