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

• Autores: Mlnoru Iwata, Shiro Maeda, Yutaka Kamura, Atsuko Takano, Hiromi Kato, Shihou Murakami, Klyohiro Hlguchi, Atsushi Takahashi, Hayato Fujita, Kazuo Hara, Kazuyuki Tobe
• Localización: Diabetes care, ISSN-e 0149-5992, Vol. 35, Nº. 8, 2012, págs. 1763-1770
• Idioma: inglés
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• Resumen

  • We evaluated the clinical usefulness of a genetic risk score (GRS) based on 14 well-established variants for type 2 diabetes. We analyzed 14 SNPs at HHEX, CDKAL1, CDKN2B, SLC30A8, KCNJ11, IGF2BP2, PPARG, TCF712, 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 ?-cell function (?-GRS) and then assessing the association between each GRS and the clinical features. 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^sup -21^). Among the subjects with type 2 diabetes, the ?-GRS was associated with individuals receiving insulin therapy (? = 0.0131, SE = 0.006, P = 0.0431), age at diagnosis (? = -0.608, SE = 0.204, P = 0.0029), fasting serum C-peptide level (? = -0.032, SE = 0.0140, P = 0.022), and C-peptide index (? = -0.031, SE = 0.012, P = 0.0125). Our data suggest that the ?-GRS is associated with reduced ?-cell functions and may be useful for selecting patients who should receive more aggressive ?-cell-preserving therapy.