Kyeong-Soo Park

Relative contribution of body composition to bone mineral density at different sites in men and women of South Korea

We examined the relative contribution of body composition to bone mineral density (BMD) at various sites in 1406 Korean rural men and women, aged 19–80 years, from July to August 2004. The BMD was measured at peripheral (distal forearm and calcaneus) and central (lumbar spine at L1–L4, femoral neck, trochanter, and Wards triangle) using dual-energy X-ray absorptiometry. In multivariate analyses, the linear regression models were adjusted for relevant covariates. In premenopausal women, only lean mass had a significant positive correlation with BMD at all sites. In postmenopausal women, fat mass was significantly positively correlated with BMD at all sites, except the Wards triangle; fat mass was the only determinant of BMD at the lumbar, distal forearm, and calcaneus sites, whereas both lean and fat mass contributed to BMD at the hip, with the effect of lean mass being slightly greater than that of fat mass. In younger men, lean mass had a significant positive contribution to BMD at all sites, whereas fat mass appeared to contribute negatively to BMD at all sites, except the calcaneus. In older men, lean mass made a significant positive contribution to the BMD at all sites; fat mass also made a significant positive contribution to the BMD at the forearm and calcaneus. These data indicate that in the Korean rural population, lean mass may be an important determinant of the BMD, whereas fat mass may contribute positively to BMD only in postmenopausal women and older men.

Association between folate-metabolizing pathway polymorphism and non-Hodgkin lymphoma

Polymorphisms in the genes coding folate‐metabolizing enzymes affect the risk of some forms of cancer. We investigated the association between these polymorphisms and non‐Hodgkin lymphoma (NHL) risk in a population‐based study (583 cases and 1700 controls). The MTHFR 677TT and CT genotypes were associated with reduced risk for NHL [odds ratios (OR) = 0·79; 95% confidence intervals (CI) = 0·65–0·98 for 677CT and 0·61; 0·45–0·82 for 677TT] and diffuse large B‐cell lymphoma (DLBCL) (OR = 0·68; 0·51–0·88 for 677CT; OR = 0·56; 0·38–0·83 for 677TT). The MTHFR 1298CC genotype was associated with increased risk for NHL (OR = 1·71; 1·07–2·75) and T‐cell lymphoma (OR = 3·05; 1·53‐6·11). The MTRR 66GG genotype was associated with increased risk for DLBCL (OR = 1·56; 1·03‐2·38) and the TYMS 2R2R genotype was associated with increased risk for T‐cell lymphoma (OR = 2·83; 1·33–6·01). Using subjects with 3RG3RG as a reference group, TYMS 2R2R was associated with increased risk for T‐cell lymphoma (OR = 2·46; 1·04–5·79). Interestingly, we observed a reduced association between the TYMS 2R3RG genotype and DLBCL (OR = 0·61; 0·38–0·99). These results suggest that MTHFR, MTRR and TYMS polymorphisms may play a significant role in the risk for NHL.

Association between polymorphisms of folate-metabolizing enzymes and hematological malignancies

Several genetic polymorphisms in the genes coding folate-metabolizing enzymes have been associated with susceptibility to hematology malignancies. We conducted a Korean population-based case-control study to examine the relationship between the polymorphisms of folate-metabolizing enzymes and the risk of AML (acute myelogenous leukemia), CML (chronic myelogenous leukemia), MDS (myelodyspastic syndrome), and ALL (acute lymphoblastc leukemia). The MTHFR 677TT genotype was associated with an increased risk for ALL (odds ratios (OR)=1.77; 95% confidence intervals (CI)=1.02-3.09, p=.044). The MTRR 66 AG genotype was associated with an increased risk for MDS (OR=1.59; 1.06-2.38, p=.026) and the MTRR 66 GG genotype was associated with increased risk for AML (OR=1.51; 1.03-2.23, p=.037). The TYMS 2R3R genotype was associated with a decreased risk for AML (OR=0.76; 0.60-0.96, p=.022). The TYMS hap3 (2R-6bp) and hap4 (2R-0bp) were associated with decreased risk (OR=0.69; 0.53-0.90, p=.006) and increased risk (OR=1.65; 1.20-2.27, p=.002), respectively for AML. Hap C (677T-1298A) was associated with an increased risk (OR=1.40; 1.02-1.92, p=.04) for ALL. The risk for ALL appears to be associated with the MTHFR 677 polymorphism. The results are supportive of a risk modification by folate polymorphisms in several hematologic malignancies in Korea. The pattern of results suggests that MDS was associated with the DNA methylation status and the risk for AML was associated with both the DNA synthesis and DNA methylation status.

Cohort Profile: The Namwon Study and the Dong-gu Study

These two cohorts were designed to examine the increasing burden of chronic diseases among Korean populations. The studies investigated determinants for stroke, osteoporosis, dementia and cancer among middle-aged and elderly Korean populations. The Namwon Study baseline survey was performed between 2004 and 2007 (n = 10 667), and followed up 4 years later (n = 8157, follow-up rate = 76.5%). The baseline survey of the Dong-gu Study was administered over 2007-2010 (n = 9260), and will be followed up between 2014 and 2015. Questionnaires included assessment of cognitive function, psychiatric health and lifestyle factors. Clinical examinations, biochemical tests and genotyping focused on evaluating the determinants of target diseases and their intermediate phenotypes. Potential collaborators will be invited to contact the chief investigators.

Prevalence of osteoporosis and reference data for lumbar spine and hip bone mineral density in a Korean population

The aims of this study were to establish reference data for bone mineral density (BMD) at central skeletal sites using Lunar dual-energy X-ray absorptiometry (DXA), and to estimate the age-and sex-specific prevalence of osteoporosis in a Korean population. We performed a population-based, cross-sectional study. The subjects were 4148 (1810 men and 2338 women) Korean adults, aged 20–79 years. The BMD for central sites (lumbar spine, femoral neck, trochanter, and Ward’s triangle) were measured by DXA. The standardized prevalence of osteoporosis among individual aged 50–79 years in lumbar spine, femoral neck, Ward’s triangle, and trochanter was 40.1%, 12.4%, 28.4%, and 4.4% in women and 6.5%, 5.9%, 3.7%, and 1.6% in men, respectively. In women, peak BMD occurred in the age range 40–49 years for the femoral neck and trochanter, 30–39 years for the lumbar spine, and 20–29 years for Ward’s triangle. In men, peak BMD values were observed at 20–29 years for all measured sites. This study establishes a normative database for BMD at central skeletal sites using dualenergy X-ray absorptiometry and provides more reliable information on the prevalence of osteoporosis in Korea.

Telomere length shortening in non-Hodgkin's lymphoma patients undergoing chemotherapy

We investigated telomere length changes in patients with non-Hodgkins lymphoma (NHL) receiving conventional-dose chemotherapy. Using Southern blot analysis, telomere length was measured in peripheral blood mononuclear cells from five NHL patients at diagnosis, 15 NHL patients after chemotherapy, and 39 healthy controls. Compared with age-matched putative normal controls, telomeres were significantly shorter in NHL patients at diagnosis. Mean telomere length was shorter after chemotherapy than before chemotherapy and was shorter after chemotherapy than in age-matched putative healthy controls. There was no correlation between the extent of telomere shortening and time elapsed after chemotherapy. These findings suggest that in NHL patients hematopoietic stem cells lose telomere length during the recovery period from bone marrow suppression after conventional-dose chemotherapy.

Distribution of the Ankle-Brachial Index and Associated Cardiovascular Risk Factors in a Population of Middle-Aged and Elderly Koreans

The Doppler ankle-brachial pressure index (ABI) is an objective and efficient tool that can be used to determine the presence and severity of peripheral arterial disease in the lower extremities. The ABI value is inversely associated with other cardiovascular risk factors. To date, there have been no studies of the distribution of ABI in Korea. We performed a cross-sectional study of 1,943 subjects (681 men and 1,262 women; 45-74 yr old) in Namwon, Korea. The prevalence of a low ABI (<0.90) was 2.2% in men and 1.8% in women, and a high ABI (≥1.30) was prevalent in 3.1% of men and 0.8% of women. Age, smoking habits, waist circumference, hypertension, and blood pressure were associated with ABI values in both sexes. The presence of carotid plaques was associated with ABI values only in men, whereas pulse pressure was associated with ABI values only in women (p<0.05). Although the prevalence of a low ABI in the present study was lower than those reported previously for Western populations and Japanese men, our results suggest that the ABI might be used as an indicator of cardiovascular risk factors in adult Koreans.

Cumulative smoking exposure, duration of smoking cessation, and peripheral arterial disease in middle-aged and older Korean men.

BackgroundWe investigated the association of cumulative smoking exposure and duration of smoking cessation with peripheral arterial disease (PAD).MethodsThe study population consisted of 2517 community-dwelling Korean men aged 50 years and older. Information on smoking characteristics such as smoking status, pack-years of smoking, and years since quitting smoking was collected using a standardized questionnaire. PAD was defined as an ankle-brachial index (ABI) less than 0.90 in either leg.ResultsThe odds ratio (OR, 95% confidence interval) of PAD was 2.31 (1.20-4.42) for former smokers and 4.30 (2.13-8.66) for current smokers, after adjusting for other cardiovascular risk factors. There was a significant dose-response relationship between pack-years of smoking and PAD. Compared with those who had never smoked, the multivariate-adjusted ORs of PAD for smokers of 0.1-20.0, 20.1-40.0, and >40.0 pack-years were 2.15 (1.06-4.38), 2.24 (1.08-4.65), and 2.93 (1.41-6.09), respectively. There was a significant decrease in PAD risk as the years since quitting smoking increased. The multivariate-adjusted ORs of PAD for 11-20 and ≥21 years smoking cessation were 0.41 (0.19-0.86) and 0.49 (0.24-0.98), compared with current smokers.ConclusionsCumulative smoking exposure and duration of smoking cessation were significantly associated with PAD in middle aged and older Korean men.

Constitution and telomere dynamics of bone marrow stromal cells in patients undergoing allogeneic bone marrow transplantation

Summary:We evaluated the genotypic origin of mesenchymal stem cells (MSC) following sex-mismatched allogeneic bone marrow transplantation (BMT), and investigated the telomere dynamics in MSC in normal individuals and patients after BMT. The study population consisted of 11 patients with hematologic disorders who showed complete chimerism after BMT. Telomere length was measured in MSC using Southern blotting analysis in eight patients and 18 healthy subjects as a control group. Following culture, MSC were identified by the expression of SH2 and SH4, and lack of CD14, CD34, and CD45. All MSC showed the recipient genotype, based on the results of fluorescent in situ hybridization analysis using X-chromosome satellite probes or microsatellite DNA polymorphism analysis. The mean telomere length in MSC from normal controls was 7.2±0.53 kb (range, 6.12–7.78), and progressive telomere shortening was seen with age. There was no significant difference in MSC telomere length between the BMT group and age-matched controls. This study confirmed that the MSC isolated from the recipients of allogeneic BMT did not have the donor genotype, despite complete chimerism. Moreover, MSC were demonstrated to show progressive loss of telomere length with age, but the telomeres in MSC were not affected by BMT.

Association of GSTT1 polymorphism with acute myeloid leukemia risk is dependent on smoking status.

Abstract Genetic polymorphisms in drug-metabolizing, DNA repair and multidrug resistance genes affect the risks for many cancers. We analyzed 21 polymorphisms in 17 genes in these pathways to evaluate their association with the risk of acute myeloid leukemia (AML) and to examine whether smoking modifies these associations in a population-based study in Korea (415 cases, 1700 controls). We found marginal associations between the risk of AML and CYP1A1 1188, and XRCC1 194, ERCC1 IVS5 + 33 and WRN 787 polymorphisms. However, when we performed the analysis according to smoking exposure, we found a stronger association for ERCC1 only in the non-smoking population (odds ratio [OR] = 0.74; 95% confidence interval [CI] = 0.60–0.91, p = 0.004), while we found the GSTT1-null genotype to be associated with an increased risk of AML in ever-smokers (OR = 1.51; 95% CI = 1.06–2.15, p = 0.02). These results indicate that ERCC1 and GSTT1-null polymorphisms may have an effect on AML risk that is dependent on smoking exposure.