Korean Diabetes J.  2010 Aug;34(4):229-236. 10.4093/kdj.2010.34.4.229.

Polymorphisms of the Reg1alpha Gene and Early Onset Type 2 Diabetes in the Korean Population

• Koo BK
• Cho YM
• Kimm K
• Lee JY
• Oh B
• Park BL
• Cheong HS
• Shin HD
• Ko KS
• Park SG
• Lee HK
• Park KS

• KMID: 2029876
• DOI: http://doi.org/10.4093/kdj.2010.34.4.229

Abstract

BACKGROUND
The Reg gene has been reported to be expressed in regenerating islets and Reg1 protein to be up-regulated at an early stage of diabetes in mice. As human Reg1alpha is homologous with murine Reg1, we investigated whether common variants in Reg1alpha are associated with type 2 diabetes in the Korean population.
METHODS
We sequenced the Reg1alpha gene to identify common polymorphisms using 24 Korean DNA samples. Of 11 polymorphisms found, five common ones (g.-385T>C [rs10165462], g.-36T>G [rs25689789], g.209G>T [rs2070707], g.1385C>G [novel], and g.2199G>A [novel]) were genotyped in 752 type 2 diabetic patients and 642 non-diabetic subjects.
RESULTS
No polymorphism was associated with the risk of type 2 diabetes. However, g.-385C and g.2199A lowered the risk of early-onset type 2 diabetes, defined as a diagnosis in subjects whose age at diagnosis was 25 years or more but less than 40 years (odds ratio [OR], 0.721 [0.535 to 0.971] and 0.731 [0.546 to 0.977] for g.-385C and g.2199A, respectively) and g.1385G increased the risk of early-onset diabetes (OR, 1.398 [1.055 to 1.854]). Although adjusting for errors in multiple hypotheses-testing showed no statistically significant association between the three individual polymorphisms and early-onset diabetes, the haplotype H1, composed of g.-385C, g.1385C, and g.2199A, was associated with a reduced risk of early-onset diabetes (OR, 0.590 [0.396 to 0.877], P = 0.009).
CONCLUSION
Polymorphisms in the Reg1alpha were not found to be associated with overall susceptibility to type 2 diabetes, though some showed modest associations with early-onset type 2 diabetes in the Korean population.

Keyword

Diabetes mellitus, type 2; Polymorphism; Reg1alpha gene

MeSH Terms

Animals
Diabetes Mellitus, Type 2
DNA
Haplotypes
Humans
Mice
DNA

Figure

• 

  Fig. 1 (A) Map of the Reg1α gene on chromosome 2p12 with polymorphisms which were identified in 24 Korean DNA samples. Single nucleotide polymorphisms in bold were selected for sequencing in all subjects. (B) Linkage disequilibrium among Reg1α polymorphisms. r2 is a measure of the correlation between alleles at two sites and is calculated by dividing by the product of the four allele frequencies at the two loci.; |D'| = D/Dmax (D represents disequilibrium coefficient and Dmax is the largest possible value of D).

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