Association between polymorphisms of the α-kinase 1 gene and type 2 diabetes mellitus in community‑dwelling individuals

Shimokata,Shigetaka; Oguri,Mitsutoshi; Fujimaki,Tetsuo; Horibe,Hideki; Kato,Kimihiko; Yamada,Yoshiji

doi:10.3892/br.2013.173

Association between polymorphisms of the α-kinase 1 gene and type 2 diabetes mellitus in community‑dwelling individuals

Authors:
- Shigetaka Shimokata
- Mitsutoshi Oguri
- Tetsuo Fujimaki
- Hideki Horibe
- Kimihiko Kato
- Yoshiji Yamada
View Affiliations

Affiliations: Department of Cardiology, Japanese Red Cross Nagoya First Hospital, Nagoya, Aichi, Japan, Department of Cardiovascular Medicine, Inabe General Hospital, Inabe, Mie, Japan, Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Gifu, Japan, Meitoh Hospital, Nagoya, Aichi, Japan, Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Mie, Japan
Published online on: September 25, 2013 https://doi.org/10.3892/br.2013.173
Pages: 940-944

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

We previously demonstrated that the α‑kinase 1 gene (ALPK1) is a susceptibility locus for chronic kidney disease in individuals with diabetes mellitus (DM) by a genome‑wide association study. Although genetic variants of ALPK1 have been associated with chronic kidney disease in individuals with DM, whether ALPK1 is a susceptibility locus for DM has not been elucidated. The purpose of the present study was to investigate a possible association of the rs2074388 (A→G, Asp565Gly) or rs2074379 (A→G, Ile732Met) variants of ALPK1 with type 2 DM in community‑dwelling individuals. The study subjects comprised 5,959 community‑dwelling individuals (495 subjects with type 2 DM and 5,464 controls) who were recruited to a population‑based cohort study in Inabe, Mie, Japan. The comparisons of allele frequencies or genotype distributions using the chi‑square test revealed that the rs2074388 and rs2074379 variants of ALPK1 were significantly associated with type 2 DM (P<0.05). A multivariable logistic regression analysis with adjustment for age, gender, body mass index and smoking status revealed that the rs2074388 (P=0.0051; odds ratio, 1.32) and rs2074379 (P=0.0058; odds ratio, 1.32) variants were significantly associated with type 2 DM. The haplotype analysis of these polymorphisms revealed that the frequency of the major haplotype, A (rs2074388)‑A (rs2074379), was significantly lower, whereas that of the minor haplotype G‑G was significantly higher in subjects with type 2 DM compared to controls. thus, ALPK1 may be a susceptible gene for type 2 DM in community‑dwelling Japanese individuals.

View Figures

View References

1	Shaw JE, Sicree RA and Zimmet PZ: Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 87:4–14. 2010. View Article : Google Scholar : PubMed/NCBI
2	Chan JC, Malik V, Jia W, et al: Diabetes in Asia: epidemiology, risk factors, and pathophysiology. JAMA. 301:2129–2140. 2009. View Article : Google Scholar : PubMed/NCBI
3	American Diabetes Association. Economic costs of diabetes in the U.S in 2012. Diabetes Care. 36:1033–1046. 2013. View Article : Google Scholar
4	Zhang P, Zhang X, Brown J, et al: Global healthcare expenditure on diabetes for 2010 and 2030. Diabetes Res Clin Pract. 87:293–301. 2010. View Article : Google Scholar : PubMed/NCBI
5	Dailey G: Early and intensive therapy for management of hyperglycemia and cardiovascular risk factors in patients with type 2 diabetes. Clin Ther. 33:665–678. 2011. View Article : Google Scholar : PubMed/NCBI
6	Look AHEAD Research Group. Wing RR, Bolin P, Brancati FL, et al: Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med. 369:145–154. 2013. View Article : Google Scholar : PubMed/NCBI
7	Valdez R: Detecting undiagnosed type 2 diabetes: family history as a risk factor and screening tool. J Diabetes Sci Technol. 3:722–726. 2009. View Article : Google Scholar : PubMed/NCBI
8	Hu FB: Globalization of diabetes: the role of diet, lifestyle, and genes. Diabetes Care. 34:1249–1257. 2011. View Article : Google Scholar : PubMed/NCBI
9	Yamauchi T, Hara K, Maeda S, et al: A genome-wide association study in the Japanese population identifies susceptibility loci for type 2 diabetes at UBE2E2 and C2CD4A–C2CD4B. Nat Genet. 42:864–868. 2010.PubMed/NCBI
10	Tabassum R, Chauhan G, Dwivedi OP, et al: Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21. Diabetes. 62:977–986. 2013. View Article : Google Scholar : PubMed/NCBI
11	Cho YS, Chen CH, Hu C, et al: Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians. Nat Genet. 44:67–72. 2011. View Article : Google Scholar : PubMed/NCBI
12	Kooner JS, Saleheen D, Sim X, et al: Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci. Nat Genet. 43:984–989. 2011. View Article : Google Scholar : PubMed/NCBI
13	Sladek R, Rocheleau G, Rung J, et al: A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature. 445:881–885. 2007. View Article : Google Scholar : PubMed/NCBI
14	Yamada Y, Nishida T, Ichihara S, et al: Identification of chromosome 3q28 and ALPK1 as susceptibility loci for chronic kidney disease in Japanese individuals by a genome-wide association study. J Med Genet. 50:410–418. 2013. View Article : Google Scholar : PubMed/NCBI
15	American Diabetes Association. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diab Care. 26(Suppl): S5–S20. 2003. View Article : Google Scholar
16	Kuzuya T, Nakagawa S, Satoh J, et al; Committee of the Japan Diabetes Society on the diagnostic criteria of diabetes mellitus. Report of the Committee on the classification and diagnosis criteria of diabetes mellitus. Diabetes Res Clin Pract. 55:65–85. 2002. View Article : Google Scholar : PubMed/NCBI
17	Itoh Y, Mizuki N, Shimada T, et al: High-throughput DNA typing of HLA-A, -B, -C, and -DRB1 loci by a PCR-SSOP-Luminex method in the Japanese population. Immunogenetics. 57:717–729. 2005. View Article : Google Scholar : PubMed/NCBI
18	Ryazanov AG, Pavur KS and Dorovkov MV: Alpha-kinases: a new class of protein kinases with a novel catalytic domain. Curr Biol. 9:R43–R45. 1999. View Article : Google Scholar : PubMed/NCBI
19	Heine M, Cramm-Behrens CI, Ansari A, et al: Alpha-kinase 1, a new component in apical protein transport. J Biol Chem. 280:25637–25643. 2005. View Article : Google Scholar : PubMed/NCBI
20	Wang SJ, Tu HP, Ko AM, et al: Lymphocyte α-kinase is a gout-susceptible gene involved in monosodium urate monohydrate-induced inflammatory responses. J Mol Med. 89:1241–1251. 2011.
21	Kahn SE: The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia. 46:3–19. 2003.
22	Fukushima M, Usami M, Ikeda M, et al: Insulin secretion and insulin sensitivity at different stages of glucose tolerance: a cross-sectional study of Japanese type 2 diabetes. Metabolism. 53:831–835. 2004. View Article : Google Scholar : PubMed/NCBI
23	Ruotsalainen E, Salmenniemi U, Vauhkonen I, et al: Changes in inflammatory cytokines are related to impaired glucose tolerance in offspring of type 2 diabetic subjects. Diab Care. 29:2714–2720. 2006. View Article : Google Scholar : PubMed/NCBI
24	Olefsky JM and Glass CK: Macrophages, inflammation, and insulin resistance. Annu Rev Physiol. 72:219–246. 2010. View Article : Google Scholar : PubMed/NCBI
25	Norlin S, Ahlgren U and Edlund H: Nuclear factor-κB activity in β-cells is required for glucose-stimulated insulin secretion. Diabetes. 54:125–132. 2005.