The association of genetic variants in Krüppel-like factor 11 and Type 2 diabetes in the Japanese population
Aims Krüppel‐like factor 11 (KLF11) is a transcriptional factor of the zinc finger domain family that regulates the expression of insulin. In North European populations, its common functional variant Q62R (rs35927125) is a strong genetic factor for Type 2 diabetes (P = 0.00033, odds ratio for G all...
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| Published in | Diabetic medicine Vol. 25; no. 1; pp. 19 - 26 |
|---|---|
| Main Authors | , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Oxford, UK
Blackwell Publishing Ltd
01.01.2008
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0742-3071 1464-5491 1464-5491 |
| DOI | 10.1111/j.1464-5491.2007.02315.x |
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| Abstract | Aims Krüppel‐like factor 11 (KLF11) is a transcriptional factor of the zinc finger domain family that regulates the expression of insulin. In North European populations, its common functional variant Q62R (rs35927125) is a strong genetic factor for Type 2 diabetes (P = 0.00033, odds ratio for G allele = 1.29, 95% CI 1.12–1.49). We examined the contribution of KLF11 variants to the susceptibility to Type 2 diabetes in a Japanese population.
Methods By re‐sequencing Japanese individuals (n = 24, partly 96), we screened all four exons, exon/intron boundaries and flanking regions of KLF11. Verified single nucleotide polymorphisms (SNPs) were genotyped in 731 initial samples (369 control and 362 case subjects). Subsequently, we tested for association in 1087 samples (524 control and 563 case subjects), which were collected in different districts of Japan from the initial samples.
Results We identified eight variants, including a novel A/C variant on intron 3, but no mis‐sense mutations. In an association study, we failed to find any significant result of SNPs (minor allele frequency 8.2–46.2%) after correcting for multiple testing. Similarly, no haplotypes were associated with Type 2 diabetes. It is notable that the G allele in rs35927125 was completely absent in 1818 Japanese individuals.
Conclusions Genetic variants in KLF11 are unlikely to have a major effect of Type 2 diabetes in the Japanese population, although they were significantly associated in North European populations. These observations might help to determine the role of KLF11 variants in Type 2 diabetes in different populations. |
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| AbstractList | Krüppel-like factor 11 (KLF11) is a transcriptional factor of the zinc finger domain family that regulates the expression of insulin. In North European populations, its common functional variant Q62R (rs35927125) is a strong genetic factor for Type 2 diabetes (P = 0.00033, odds ratio for G allele = 1.29, 95% CI 1.12-1.49). We examined the contribution of KLF11 variants to the susceptibility to Type 2 diabetes in a Japanese population.AIMSKrüppel-like factor 11 (KLF11) is a transcriptional factor of the zinc finger domain family that regulates the expression of insulin. In North European populations, its common functional variant Q62R (rs35927125) is a strong genetic factor for Type 2 diabetes (P = 0.00033, odds ratio for G allele = 1.29, 95% CI 1.12-1.49). We examined the contribution of KLF11 variants to the susceptibility to Type 2 diabetes in a Japanese population.By re-sequencing Japanese individuals (n = 24, partly 96), we screened all four exons, exon/intron boundaries and flanking regions of KLF11. Verified single nucleotide polymorphisms (SNPs) were genotyped in 731 initial samples (369 control and 362 case subjects). Subsequently, we tested for association in 1087 samples (524 control and 563 case subjects), which were collected in different districts of Japan from the initial samples.METHODSBy re-sequencing Japanese individuals (n = 24, partly 96), we screened all four exons, exon/intron boundaries and flanking regions of KLF11. Verified single nucleotide polymorphisms (SNPs) were genotyped in 731 initial samples (369 control and 362 case subjects). Subsequently, we tested for association in 1087 samples (524 control and 563 case subjects), which were collected in different districts of Japan from the initial samples.We identified eight variants, including a novel A/C variant on intron 3, but no mis-sense mutations. In an association study, we failed to find any significant result of SNPs (minor allele frequency 8.2-46.2%) after correcting for multiple testing. Similarly, no haplotypes were associated with Type 2 diabetes. It is notable that the G allele in rs35927125 was completely absent in 1818 Japanese individuals.RESULTSWe identified eight variants, including a novel A/C variant on intron 3, but no mis-sense mutations. In an association study, we failed to find any significant result of SNPs (minor allele frequency 8.2-46.2%) after correcting for multiple testing. Similarly, no haplotypes were associated with Type 2 diabetes. It is notable that the G allele in rs35927125 was completely absent in 1818 Japanese individuals.Genetic variants in KLF11 are unlikely to have a major effect of Type 2 diabetes in the Japanese population, although they were significantly associated in North European populations. These observations might help to determine the role of KLF11 variants in Type 2 diabetes in different populations.CONCLUSIONSGenetic variants in KLF11 are unlikely to have a major effect of Type 2 diabetes in the Japanese population, although they were significantly associated in North European populations. These observations might help to determine the role of KLF11 variants in Type 2 diabetes in different populations. Aims Krüppel‐like factor 11 ( KLF11 ) is a transcriptional factor of the zinc finger domain family that regulates the expression of insulin. In North European populations, its common functional variant Q62R (rs35927125) is a strong genetic factor for Type 2 diabetes ( P = 0.00033, odds ratio for G allele = 1.29, 95% CI 1.12–1.49). We examined the contribution of KLF11 variants to the susceptibility to Type 2 diabetes in a Japanese population. Methods By re‐sequencing Japanese individuals ( n = 24, partly 96), we screened all four exons, exon/intron boundaries and flanking regions of KLF11 . Verified single nucleotide polymorphisms (SNPs) were genotyped in 731 initial samples (369 control and 362 case subjects). Subsequently, we tested for association in 1087 samples (524 control and 563 case subjects), which were collected in different districts of Japan from the initial samples. Results We identified eight variants, including a novel A/C variant on intron 3, but no mis‐sense mutations. In an association study, we failed to find any significant result of SNPs (minor allele frequency 8.2–46.2%) after correcting for multiple testing. Similarly, no haplotypes were associated with Type 2 diabetes. It is notable that the G allele in rs35927125 was completely absent in 1818 Japanese individuals. Conclusions Genetic variants in KLF11 are unlikely to have a major effect of Type 2 diabetes in the Japanese population, although they were significantly associated in North European populations. These observations might help to determine the role of KLF11 variants in Type 2 diabetes in different populations. Aims Krüppel‐like factor 11 (KLF11) is a transcriptional factor of the zinc finger domain family that regulates the expression of insulin. In North European populations, its common functional variant Q62R (rs35927125) is a strong genetic factor for Type 2 diabetes (P = 0.00033, odds ratio for G allele = 1.29, 95% CI 1.12–1.49). We examined the contribution of KLF11 variants to the susceptibility to Type 2 diabetes in a Japanese population. Methods By re‐sequencing Japanese individuals (n = 24, partly 96), we screened all four exons, exon/intron boundaries and flanking regions of KLF11. Verified single nucleotide polymorphisms (SNPs) were genotyped in 731 initial samples (369 control and 362 case subjects). Subsequently, we tested for association in 1087 samples (524 control and 563 case subjects), which were collected in different districts of Japan from the initial samples. Results We identified eight variants, including a novel A/C variant on intron 3, but no mis‐sense mutations. In an association study, we failed to find any significant result of SNPs (minor allele frequency 8.2–46.2%) after correcting for multiple testing. Similarly, no haplotypes were associated with Type 2 diabetes. It is notable that the G allele in rs35927125 was completely absent in 1818 Japanese individuals. Conclusions Genetic variants in KLF11 are unlikely to have a major effect of Type 2 diabetes in the Japanese population, although they were significantly associated in North European populations. These observations might help to determine the role of KLF11 variants in Type 2 diabetes in different populations. Krüppel-like factor 11 (KLF11) is a transcriptional factor of the zinc finger domain family that regulates the expression of insulin. In North European populations, its common functional variant Q62R (rs35927125) is a strong genetic factor for Type 2 diabetes (P = 0.00033, odds ratio for G allele = 1.29, 95% CI 1.12-1.49). We examined the contribution of KLF11 variants to the susceptibility to Type 2 diabetes in a Japanese population. By re-sequencing Japanese individuals (n = 24, partly 96), we screened all four exons, exon/intron boundaries and flanking regions of KLF11. Verified single nucleotide polymorphisms (SNPs) were genotyped in 731 initial samples (369 control and 362 case subjects). Subsequently, we tested for association in 1087 samples (524 control and 563 case subjects), which were collected in different districts of Japan from the initial samples. We identified eight variants, including a novel A/C variant on intron 3, but no mis-sense mutations. In an association study, we failed to find any significant result of SNPs (minor allele frequency 8.2-46.2%) after correcting for multiple testing. Similarly, no haplotypes were associated with Type 2 diabetes. It is notable that the G allele in rs35927125 was completely absent in 1818 Japanese individuals. Genetic variants in KLF11 are unlikely to have a major effect of Type 2 diabetes in the Japanese population, although they were significantly associated in North European populations. These observations might help to determine the role of KLF11 variants in Type 2 diabetes in different populations. |
| Author | Nakamura, N. Moritani, M. Yoshikawa, T. Keshavarz, P. Yamaguchi, Y. Itakura, M. Inoue, H. Miyawaki, K. Shiota, H. Shinohara, K. Kunika, K. Tanahashi, T. |
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– ident: e_1_2_8_25_2 doi: 10.1007/s00125-006-0353-x – ident: e_1_2_8_9_2 doi: 10.2337/diabetes.52.2.568 – ident: e_1_2_8_5_2 doi: 10.1038/nm738 – ident: e_1_2_8_6_2 doi: 10.1053/j.gastro.2004.05.018 – ident: e_1_2_8_20_2 doi: 10.2337/diabetes.53.4.1134 |
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| Snippet | Aims Krüppel‐like factor 11 (KLF11) is a transcriptional factor of the zinc finger domain family that regulates the expression of insulin. In North European... Aims Krüppel‐like factor 11 ( KLF11 ) is a transcriptional factor of the zinc finger domain family that regulates the expression of insulin. In North European... Krüppel-like factor 11 (KLF11) is a transcriptional factor of the zinc finger domain family that regulates the expression of insulin. In North European... |
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| SubjectTerms | Adult Analysis of Variance Asian Continental Ancestry Group - genetics association study Cell Cycle Proteins - analysis Cell Cycle Proteins - genetics Diabetes Mellitus, Type 2 - genetics Female Gene Frequency Genetic Predisposition to Disease Genotype Humans Insulin - metabolism Insulin Secretion Japan - ethnology Japanese KLF11 Linkage Disequilibrium Male Middle Aged Original : Genetics Repressor Proteins - analysis Repressor Proteins - genetics Type 2 diabetes |
| Title | The association of genetic variants in Krüppel-like factor 11 and Type 2 diabetes in the Japanese population |
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