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.

Abstract

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.

• Authors: Minoru Iwata, Shiro Maeda, Yutaka Kamura, Atsuko Takano, Hiromi Kato, Shihou Murakami, Kiyohiro Higuchi, Atsushi Takahashi, Hayato Fujita, Kazuo Hara, Takashi Kadowaki, Kazuyuki Tobe
• Journal: Diabetes care (Diabetes Care) Vol. 35 Issue 8 Pg. 1763-70 (Aug 2012) ISSN: 1935-5548 [Electronic] United States
• PMID: 22688542 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• CDKN2B protein, human
• Cation Transport Proteins
• Cyclin-Dependent Kinase Inhibitor p15
• GCKR protein, human
• HHEX protein, human
• Homeodomain Proteins
• IRS1 protein, human
• Insulin
• Insulin Receptor Substrate Proteins
• KCNQ1 Potassium Channel
• Kir6.2 channel
• PPAR gamma
• Potassium Channels, Inwardly Rectifying
• Proteins
• SLC30A8 protein, human
• Transcription Factor 7-Like 2 Protein
• Transcription Factors
• Zinc Transporter 8
• Alpha-Ketoglutarate-Dependent Dioxygenase FTO
• FTO protein, human
• tRNA Methyltransferases
• UBE2E2 protein, human
• Ubiquitin-Conjugating Enzymes
• Cyclin-Dependent Kinase 5
• CDKAL1 protein, human

Topics

• Adaptor Proteins, Signal Transducing (genetics)
• Age of Onset
• Aged
• Alleles
• Alpha-Ketoglutarate-Dependent Dioxygenase FTO
• Asian People
• Cation Transport Proteins (genetics)
• Cyclin-Dependent Kinase 5 (genetics)
• Cyclin-Dependent Kinase Inhibitor p15 (genetics)
• Diabetes Mellitus, Type 2 (epidemiology, genetics)
• Female
• Genetic Predisposition to Disease (genetics)
• Homeodomain Proteins (genetics)
• Humans
• Insulin (therapeutic use)
• Insulin Receptor Substrate Proteins (genetics)
• KCNQ1 Potassium Channel (genetics)
• Male
• Middle Aged
• PPAR gamma (genetics)
• Polymorphism, Single Nucleotide (genetics)
• Potassium Channels, Inwardly Rectifying (genetics)
• Proteins (genetics)
• Transcription Factor 7-Like 2 Protein (genetics)
• Transcription Factors (genetics)
• Ubiquitin-Conjugating Enzymes (genetics)
• Zinc Transporter 8
• tRNA Methyltransferases