Common variants at the GCK, GCKR, G6PC2–ABCB11 and MTNR1B loci are associated with fasting glucose in two Asian populations
pmid: 19937311
Common variants at the GCK, GCKR, G6PC2–ABCB11 and MTNR1B loci are associated with fasting glucose in two Asian populations
To test fasting glucose association at four loci recently identified or verified by genome-wide association (GWA) studies of European populations, we performed a replication study in two Asian populations.We genotyped five common variants previously reported in Europeans: rs1799884 (GCK), rs780094 (GCKR), rs560887 (G6PC2-ABCB11) and both rs1387153 and rs10830963 (MTNR1B) in the general Japanese (n = 4,813) and Sri Lankan (n = 2,319) populations. To identify novel variants, we further examined genetic associations near each locus by using GWA scan data on 776 non-diabetic Japanese samples.Fasting glucose association was replicated for the five single nucleotide polymorphisms (SNPs) at p < 0.05 (one-tailed test) in South Asians (Sri Lankan) as well as in East Asians (Japanese). In fine-mapping by GWA scan data, we identified in the G6PC2-ABCB11 region a novel SNP, rs3755157, with significant association in Japanese (p = 2.6 x 10(-8)) and Sri Lankan (p = 0.001) populations. The strength of association was more prominent at rs3755157 than that of the original SNP rs560887, with allelic heterogeneity detected between the SNPs. On analysing the cumulative effect of associated SNPs, we found the per-allele gradients (beta = 0.055 and 0.069 mmol/l in Japanese and Sri Lankans, respectively) to be almost equivalent to those reported in Europeans.Fasting glucose association at four tested loci was proven to be replicable across ethnic groups. Despite this overall consistency, ethnic diversity in the pattern and strength of linkage disequilibrium certainly exists and can help to appreciably reduce potential causal variants after GWA studies.
- Nagoya University Japan
- Kyushu University Japan
- Osaka Gakuin University Japan
- Osaka University Japan
- University of Kelaniya Sri Lanka
Blood Glucose, Receptor, Melatonin, MT2, Chromosome Mapping, Genetic Variation, Fasting, Protein Serine-Threonine Kinases, Polymorphism, Single Nucleotide, Germinal Center Kinases, Asian People, Haplotypes, Japan, Ethnicity, Glucose-6-Phosphatase, Humans, Regression Analysis, ATP-Binding Cassette Transporters, ATP Binding Cassette Transporter, Subfamily B, Member 11, Alleles, Adaptor Proteins, Signal Transducing, Sri Lanka
Blood Glucose, Receptor, Melatonin, MT2, Chromosome Mapping, Genetic Variation, Fasting, Protein Serine-Threonine Kinases, Polymorphism, Single Nucleotide, Germinal Center Kinases, Asian People, Haplotypes, Japan, Ethnicity, Glucose-6-Phosphatase, Humans, Regression Analysis, ATP-Binding Cassette Transporters, ATP Binding Cassette Transporter, Subfamily B, Member 11, Alleles, Adaptor Proteins, Signal Transducing, Sri Lanka
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