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Sulfotransferase 1E1 (SULT1E1) catalyze estrogen into sulfate conjugation and is involved in the metabolism of phytoestrogen. A community-based cross-sectional study was conducted on 397 Korean women, to evaluate the association between genetic polymorphisms of SULT1E1 and bone mineral density (BMD) and the combined effect of the genetic polymorphism and phytoestrogen intake for BMD in Korean women. BMDs of the distal radius and the calcaneus were measured by dual-energy X-ray absorptiometry. Genotypes of SULT1E1 IVS1-447 C>A, IVS4-1653 T>C, and *959 G>A were determined by the 5'-nuclease assay (TaqMan). Phytoestrogen intake was estimated by a food-frequency questionnaire validated against multiple 24-hour recalls. Women with the SULT1E1 *959 GG genotype had a 4.5% lower BMD at the distal radius (P (trend )= 0.05) and a 7.9% lower BMD at the calcaneus compared to those with AA genotype (P (trend) < 0.01), whereas the SULT1E1 IVS1-447 CC genotype and IVS4-1653 TT genotype were not associated with BMD. There was no significant trend of BMD with the numbers of CTG-containing haplotypes, but calcaneal BMDs significantly differed between SULT1E1 CTA-CTA haplotype and CTG-CCA haplotype (P < 0.05). When stratified by SULT1E1 genotype, the correlation between phytoestrogen consumption and BMD at the calcaneus was noteworthy in women with SULT1E1 *959 GG genotype (r = 0.25, P = 0.01) or SULT1E1 IVS 4-1653 TT genotype (r = 0.15, P = 0.02). This trend remained significant only in postmenopausal women (r = 0.36, P = 0.01) after multiple testing was corrected by the false discovery rate method. In conclusion, the genetic polymorphism of SULT1E1 *959 G > A was associated with BMD at the distal radius and calcaneus, and the association between phytoestrogen consumption and calcaneal BMD might be modified by this genetic polymorphism.

Bone morphogenetic proteins (BMPs) play critical roles in osteoblast differentiation. To investigate the association between common single-nucleotide polymorphisms (SNPs) of BMPs and bone mineral density (BMD), a cross-sectional study was conducted in healthy Korean men (n = 237) and women (n = 276) aged 20-39 years. Calcaneus and distal radius BMD were measured by dual energy X-ray absorptiometry. SNPs of BMP2 (-1103C > A, c.584G > A, IVS1-2744A > G, c.893T > A), BMP4 (c.712T > C, IVS1-160C > T), and BMP6 (c.1283C > G, IVS4-6838A > G, IVS5 + 24C > T) were determined using the 5'-nuclease assay. Significant associations were observed between BMP2 c.584G > A, c.893T > A genotypes and male calcaneus as well as female distal radius BMD. Men with the BMP2 c.893 AA genotype had a 16% higher BMD at the calcaneus (P for trend = 0.014), whereas women with this genotype had a 7% lower BMD at the distal radius than the other genotypes (P for trend = 0.010). A significant association was also observed between BMP4 IVS1-160C > T and male calcaneus BMD (P for trend = 0.024). When the association between haplotypes and BMD was investigated, the AAGA haplotype of BMP2 was significantly associated with low bone mass in female distal radius (P for trend = 0.013). These results suggested that one or more SNPs of BMP2 and BMP4 are associated with peripheral BMD in Korean men and women. However, this association is dependent on anatomical sites and gender. Thus, larger studies with complete coverage of SNPs are needed in the future.

To evaluate the effects of genetic polymorphisms of OPG, RANK, and ESR1, which regulate osteoclastogenesis, on bone mineral density (BMD), a cross-sectional study was conducted in 650 Korean postmenopausal women. BMDs of the distal radius and the calcaneus were measured by dual energy X-ray absorptiometry (DXA). Genetic polymorphisms of OPG 163 A > G, 1181 G > C; RANK 421 C > T, 575 T > C; and ESR1 1335 C > T, 2142 G > A were determined by matrix-assisted laser desorption/ionization-time of flight (MALDI-ToF) mass spectrometry. The differences between the BMDs of the genotypes of OPG, RANK, and ESR1 were analyzed by multiple linear regression model adjusted for age and body mass index. Women with the OPG 1181 CC genotype had higher BMDs at the distal radius (7%) and calcaneus (10%) than those with the GG genotype; and these differences were statistically significant (P = 0.001 and P = 0.007, respectively). A significant association was also observed between RANK 575 T > C and calcaneus BMD (P for trend = 0.017). No significant association was observed between BMDs and the polymorphisms of ESR1. The association between OPG 1181 G > C and BMD was profound in subjects with the RANK 575 TT or ESR1 2142 GG genotypes; women with OPG 1181 CC had higher BMDs at the distal radius (11%) and calcaneus (11%) than those with OPG 1181 GG only in women with RANK 575 TT genotype (P = 0.002 and P = 0.021, respectively). These results suggest that OPG genetic polymorphisms, especially with the RANK 575 TT or ESR1 2142 GG genotypes, are related to low BMD in postmenopausal Korean women.

Objectives: To compare the prevalence and metabolic profiles of glucose tolerance categories according to World Health Organization(WHO) and 1997 American Diabetes Association(ADA) fasting criteria for the diagnosis of diabetes mellitus and impaired glucose metabolism in the Korean population., Methods: 2251 subjects without previous history of diabetes, who participated in the Yonchon diabetes epidemiology survey in 1993, were classified according to both criteria. The prevalence of glucose tolerance categories and the agreement across all categories of glucose tolerance were calculated. Metabolic characteristics of different glucose tolerance categories were compared., Results: The prevalence of diabetes and impaired fasting glucose(IFG) according to ADA fasting criteria was similar to those of diabetes and impaired glucose tolerance(IGT) according to WHO criteria, respectively. However, 35.5% of the subjects who were diagnosed as diabetes by WHO criteria were reclassified as either IFG or normal fasting glucose (NFG), and 38.5% of diabetic patients according to ADA fasting criteria were IGT or normal glucose tolerance (NGT) by WHO criteria. Only 31.3% of IGT subjects remained as IFG and 62.1% were reclassified as NFG. Similarly, 69.4% of IFG subjects were NGT by WHO criteria. The agreement between the two criteria was poor (K = 0.31). Discordant diabetes groups had higher WHR, systolic and diastolic blood pressure, cholesterol and triglyceride levels than concordant non-diabetes group. Non-diabetes(WHO)/diabetes(ADA) group had higher WHR than diabetes (WHO)/non-diabetes(ADA) group. There were no differences in other metabolic characteristics between the two discordant diabetes groups. IGT/NFG and NGT/IFG group showed higher BMI, WHR, systolic and diastolic blood pressure, cholesterol and triglyceride levels than NGT/NFG group. Metabolic characteristics of IGT/NFG group were not different from those of NGT/IFG group except IGT/NFG subjects were older than NGT/IFG subjects., Conclusion: The agreement between WHO and ADA fasting criteria was poor. ADA fasting criteria can detect new diabetic patients and subjects with impaired glucose metabolism who are not classified as diabetes or IGT by WHO criteria. However, a substantial number of subjects, who may have increased cardiovascular risk and/or increased risk for the development of diabetes and its complication, will be missed when using ADA fasting criteria.

Mitochondrial tRNA(Leu)(UUR) gene mutation is one of the candidates in the pathogenesis of NIDDM. Especially the 3243 (A-->G) mutation is associated with the maternally-inherited diabetes and deafness. To evaluate the prevalence and characteristics of the 3243 point mutation in Koreans, we screened 433 Korean diabetic patients (220 men and 213 women). Genomic DNA was extracted from peripheral white blood cells and PCR was carried out with mitochondrial DNA primers (3130-3149, 3558-3539) encompassing the 3243 position. After digestion with Apa-1, five subjects showed polymorphism suggesting 3243 point mutation but when we directly sequenced the amplified DNA with an automatic sequencer, only 2 of the 5 patients were shown to have 3243 (A-->G) mutation and the other 3 subjects had 3426 (A-->G) mutation rather than 3243 mutation. Two diabetic patients with 3243 mutation were lean (BMI = 14.4, 17.0 kg/m2), had relatively lower fasting C-peptide concentrations (0.9 ng/ml each), and required insulin for management. In contrast, those with 3426 point mutation were not lean (BMI = 22.6-28.0 kg/m2), had relatively higher C-peptide levels (3.9-5.4 ng/ml), and could be managed with oral hypoglycemic agents. None of the 5 patients had deafness. In conclusion, the prevalence of 3243 point mutation in Korean diabetic patients was approximately 0.5% and we found a new mutation mimicking 3243 mutation by PCR-RFLP (restriction fragment length polymorphism) pattern. We suggest that sequencing of the PCR product or designing smaller PCR fragment size to enhance the specificity may help to identify the exact location of the point mutation.

Objective: To determine the risk factors for the development of NIDDM in Yonchon County of Korea., Research Design and Methods: We studied 1,193 Korean nondiabetic subjects at baseline who participated in a 2-year follow-up study on diabetes in Yonchon County. A 75-g oral glucose tolerance test was performed 2 years after the baseline examination. Age, sex, and anthropometric and metabolic characteristics at baseline were analyzed simultaneously as potential predictors of conversion to NIDDM. We also designed a nested case-control study to determine the role of hyperinsulinemia and/or hyperproinsulinemia in the conversion to NIDDM in patients with newly developed diabetes and control subjects matched for age, sex, BMI, and waist-to-hip-ratio., Results: At 2 years, 67 subjects developed diabetes, as defined by World Health Organization criteria. The age-adjusted incidence was significantly higher in men (6.4%) than in women (3.0%), and the incidence increased as age increased in both sexes. Multiple logistic regression analysis revealed age, male sex, and fasting and 2-h glucose levels to be significant risk factors for the development of NIDDM, whereas waist-to-hip ratio and BMI were not. In a nested case-control study, baseline proinsulin but not insulin levels were significantly higher in subjects who progressed to NIDDM than in those who did not., Conclusions: In the Korean population, beta-cell dysfunction, as measured by high proinsulin levels, seems to be associated with subsequent development of NIDDM, whereas regional and general obesity and fasting insulin levels, which may be a surrogate for insulin resistance, were not.