Journal List > J Korean Diabetes Assoc > v.30(1) > 1062365

Lee, Kwak, Jo, Choi, Shin, Moon, Cho, Jang, Park, Kim, and Lee: Association between Genetic Polymorphisms in Hepatocyte Nuclear Factor 4α and Type 2 Diabetes in Koreans

Abstract

Background

Hepatocyte nuclear factor-4α (HNF-4α) is a member of transcription factor network which is essential for the development and function of the beta cell. Furthermore mutations in the HNF-4α gene have been known to cause maturity-onset diabetes of the young. Therefore we aimed to examine the association between polymorphisms in the HNF-4α gene and the risk of type 2 diabetes (T2DM) and its related phenotypes in the Korean population.

Methods

Two single nucleotide polymorphisms (SNPs) in the HNF-4α gene, g.4681C>T and HNF-4α g.12352C>T (Thr139Ile), were genotyped in unrelated T2DM (n=760) and non-diabetic subjects (n=303) . The genetic associations between these SNPs and the risk of T2DM and metabolic phenotypes were analyzed.

Results

There was no significant association between genetic polymorphisms in the HNF-4α and the risk of T2DM. However HNF-4α g.4681C>T increased total cholesterol in the recessive model (P = 0.02) and showed marginal association with fasting plasma glucose (P = 0.049) in the additive model.

Conclusion

There was no significant association between genetic polymorphisms and the risk of T2DM in the Korean populations. But HNF-4α g.4681C>T was associated with higher level of total cholesterol and fasting plasma glucose.

Figures and Tables

Fig. 1
Map of polymorphisms in the HNF-4α gene and Haplotype.
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Table 1
Clinical Characteristics in Diabetes and Control
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HOMA-IR Homeostasis model assessment of insulin resistance

HDL high-density-lipoprotein

Table 2
Genotype Frequencies of g.12352C>T and g.4681C>T
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Genotype distributions, odd ratio (95% confidential interval), and p values for logistic analysis of three alternative models (Additive, dominant, and recessive), controlling age and sex as co-variables, are shown.

Table 3
Frequency of haplotypes in the HNF-4α
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Table 4
Clinical Characteristics according to HNF 4-α Polymorphism
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BMI body mass index, HOMA-IR homeostasis model assessment of insulin resistance, FPG fasting plasma glucose

*Common/common allele (homozygote)

Common/rare allele (heterozygote)

Rare/Rare allele (homozygote)

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