Abstract
BackgroundSeveral genome-wide association studies (GWAS) for serum fasting glucose levels have reported HHEX as possibly causal. The objective of this study was to examine the joint effect of smoking on the association of diabetes with the HHEX rs5015480 polymorphism among Korean subjects.MethodsThis replication study included a total of 4240 individuals, and multivariate linear regression and multiple logistic regression models were used. We examined the combined effect of smoking on the relationship between HHEX rs5015480 and diabetes.ResultsThe rs5015480 SNP in the HHEX gene was related to the mean FBS level (effect per allele, 1.572 mg/dL, p = 0.0122). Females with the CC genotype had a 2.68 times higher (range, 1.05–6.82 times) risk of diabetes than those with the TT/TC genotype. Although the association was stronger in female subjects (OR, 4.46; 95% CI, 1.15–17.3, p = 0.0304) among healthy individuals (N = 2461), the association between HHEX and diabetes was much stronger in male heavy smokers (OR, 4.03; 95% CI, 1.19–13.6, p = 0.0247) than in nonsmokers (p = 0.9709) and ex-smokers (p = 0.2399). The interaction of smoking was also statistically significant (P for interaction =0.0182).ConclusionsThis study clearly demonstrates that a genetic variant in HHEX influences fasting glucose levels in Korean women and male heavy smokers.
Highlights
Several genome-wide association studies (GWAS) for serum fasting glucose levels have reported hematopoietically expressed homeobox (HHEX) as possibly causal
The serum fasting glucose level is a basic indicator of diabetes [1], and several genome-wide association studies (GWAS) examining type 2 diabetes have reported that the hematopoietically expressed homeobox (HHEX) (MIM 604420) gene is a candidate causal gene [2, 3]
The rs5015480 Single nucleotide polymorphism (SNP) in the HHEX gene was related to a mean fasting blood sugar (FBS) level
Summary
Several genome-wide association studies (GWAS) for serum fasting glucose levels have reported HHEX as possibly causal. The serum fasting glucose level is a basic indicator of diabetes [1], and several genome-wide association studies (GWAS) examining type 2 diabetes have reported that the hematopoietically expressed homeobox (HHEX) (MIM 604420) gene is a candidate causal gene [2, 3]. Recent studies have shown that the HHEX rs5015480 SNP was related to serum fasting glucose levels or type 2 diabetes [4,5,6,7,8,9]. In a recent meta-analysis, the rs5015480 SNP was associated with fasting glucose (p = 0.015) [4] Another recent study in the Greek-Cypriot population reported that the rs5015480 SNP was related to type 2 diabetes (p = 0.002) [6]. The relationship between the HHEX rs5015480 polymorphism and cardiovascular disease was examined
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