Genetic Risk Score Constructed Using 14 Susceptibility Alleles for Type 2 Diabetes Is Associated With the Early Onset of Diabetes and May Predict the Future Requirement of Insulin Injections Among Japanese Individuals
| Autor: | Hiromi Kato, Minoru Iwata, Atsuko Takano, Shiro Maeda, Kazuo Hara, Takashi Kadowaki, Shihou Murakami, Atsushi Takahashi, Yutaka Kamura, Kiyohiro Higuchi, Kazuyuki Tobe, Hayato Fujita |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Oncology
Male Endocrinology Diabetes and Metabolism medicine.medical_treatment Type 2 diabetes 0302 clinical medicine Insulin Age of Onset Cation Transport Proteins Original Research 0303 health sciences tRNA Methyltransferases SLC30A8 biology Middle Aged 3. Good health KCNQ1 Potassium Channel Female Transcription Factor 7-Like 2 Protein medicine.medical_specialty Alpha-Ketoglutarate-Dependent Dioxygenase FTO 030209 endocrinology & metabolism Single-nucleotide polymorphism Zinc Transporter 8 Polymorphism Single Nucleotide 03 medical and health sciences Asian People Diabetes mellitus Internal medicine Internal Medicine medicine Humans Genetic Predisposition to Disease Potassium Channels Inwardly Rectifying Pathophysiology/Complications CDKAL1 Alleles 030304 developmental biology Adaptor Proteins Signal Transducing Aged Cyclin-Dependent Kinase Inhibitor p15 Advanced and Specialized Nursing Homeodomain Proteins business.industry fungi Proteins Cyclin-Dependent Kinase 5 medicine.disease PPAR gamma Endocrinology Diabetes Mellitus Type 2 Ubiquitin-Conjugating Enzymes biology.protein Insulin Receptor Substrate Proteins Age of onset business TCF7L2 Transcription Factors |
| Zdroj: | Diabetes Care |
| ISSN: | 1935-5548 0149-5992 |
| Popis: | OBJECTIVE We evaluated the clinical usefulness of a genetic risk score (GRS) based on 14 well-established variants for type 2 diabetes. RESEARCH DESIGN AND METHODS We analyzed 14 SNPs at HHEX, CDKAL1, CDKN2B, SLC30A8, KCNJ11, IGF2BP2, PPARG, TCF7L2, FTO, KCNQ1, IRS-1, GCKR, UBE2E2, and C2CD4A/B in 1,487 Japanese individuals (724 patients with type 2 diabetes and 763 control subjects). A GRS was calculated according to the number of risk alleles by counting all 14 SNPs (T-GRS) as well as 11 SNPs related to β-cell function (β-GRS) and then assessing the association between each GRS and the clinical features. RESULTS Among the 14 SNPs, 4 SNPs were significantly associated with type 2 diabetes in the present Japanese sample (P < 0.0036). The T-GRS was significantly associated with type 2 diabetes (P = 5.9 × 10−21). Among the subjects with type 2 diabetes, the β-GRS was associated with individuals receiving insulin therapy (β = 0.0131, SE = 0.006, P = 0.0431), age at diagnosis (β = −0.608, SE = 0.204, P = 0.0029), fasting serum C-peptide level (β = −0.032, SE = 0.0140, P = 0.022), and C-peptide index (β = −0.031, SE = 0.012, P = 0.0125). CONCLUSIONS Our data suggest that the β-GRS is associated with reduced β-cell functions and may be useful for selecting patients who should receive more aggressive β-cell–preserving therapy. |
| Databáze: | OpenAIRE |
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