Abstract
The objective of this study is to find single nucleotide polymorphisms (SNPs) associated with a risk of Type 2 diabetes (T2D) in Korean adults and to investigate the longitudinal association between these SNPs and T2D and the interaction effects of iron intake and average hemoglobin level. Data from the KoGES_Ansan and Ansung Study were used. Gene-iron interaction analysis was conducted using a two-step approach. To select candidate SNPs associated with T2D, a total of 7,935 adults at baseline were included in genome-wide association analysis (step one). After excluding T2D prevalent cases, prospective analyses were conducted with 7,024 adults aged 40–69 (step two). The association of selected SNPs and iron status with T2D and their interaction were determined using a Cox proportional hazard model. A total of 3 SNPs [rs9465871 (CDKAL1), rs10761745 (JMJD1C), and rs163177 (KCNQ1)] were selected as candidate SNPs related to T2D. Among them, rs10761745 (JMJD1C) and rs163177 (KCNQ1) were prospectively associated with T2D. High iron intake was also prospectively associated with the risk of T2D after adjusting for covariates. Average hemoglobin level was positively associated with T2D after adjusting for covariates in women. We also found significant interaction effects between rs10761745 (JMJD1C) and average hemoglobin levels on the risk of T2D among women with normal inflammation and without anemia at baseline. In conclusion, KCNQ1 and JMJD1C may prospectively contribute to the risk of T2D incidence among adults over the age of 40 and JMJD1C, but CDKAL1 may not, and iron status may interactively contribute to T2D incidence in women.
Highlights
Diabetes is a huge and growing problem
While the association between CDKAL1 and Type 2 diabetes (T2D) has been well known in Genome-wide association studies (GWAS) study using prevalent cases [31, 32] and KCNQ1 was identified as a T2D susceptibility gene in Asian and European populations [33, 34], there was no evidence on the association between JMJD1C and T2D
Among the three single nucleotide polymorphisms (SNPs) from sets 1 and 2, CDKAL1 was not associated with incident risk of T2D, but the JMJD1C polymorphism in the rs10761745 region (C>G) (HR = 0.82 and P = 5.30x10-5) and the KCNQ1 polymorphism in the rs163177 region (T>C) were significantly associated with an increased risk of T2D (HR = 1.17 and P = 6.25x10-4)
Summary
Diabetes is a huge and growing problem. The worldwide prevalence of diabetes in those aged 20–79 years was estimated to be 8.3% in 2011[1], including approximately 12.4% of Koreans aged ! 30 years [2]. The worldwide prevalence of diabetes in those aged 20–79 years was estimated to be 8.3% in 2011[1], including approximately 12.4% of Koreans aged ! It has been estimated that the number of diabetic patients worldwide will reach 439 million adults by 2030, primarily due to population growth, lifestyle, and demographic changes [3]. Excessive iron levels helps produce and amplify free radicals, which can lead to tissue damage [4]. With the exception of direct tissue damage, elevated oxidative stress may directly lead to increased blood glucose levels [6]. Increased heme iron intake is significantly associated with a greater risk of Type 2 diabetes (T2D) [7]. Higher hemoglobin level is associated with a high risk of T2D in women [9]
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