Effect of CYP3A4 metabolism on sex differences in the pharmacokinetics and pharmacodynamics of zolpidem.

To investigate pharmacokinetic and pharmacodynamic differences of zolpidem between males and females and their causes, including CYP3A4 activity. A single oral dose of zolpidem (10 mg) was administered to 15 male and 15 female healthy subjects. Blood samples were collected up to 12 h post-dose to determine plasma zolpidem concentrations. Pharmacokinetic parameters were obtained using non-compartmental analysis. Digit symbol substitution test, choice reaction time, and visual analog scale of sleepiness were used to evaluate pharmacodynamics. We measured CYP3A4 activity using 4ß-hydroxycholesterol, an endogenous metabolite. Mean maximum plasma concentration and area under the plasma concentration-time curve were higher for females than for males (9.9% and 32.5%, respectively); other pharmacokinetic parameters showed no significant differences. Pharmacodynamic scores for females showed delayed recovery compared with that for males. CYP3A4 activity was higher in females than in males (p = 0.030). There was no serious adverse event, and adverse event incidence was not different between the sexes. Zolpidem exposure was about 30% higher in females than in males. Delayed pharmacodynamic score recovery in females could be related to higher zolpidem concentrations. Although apparent clearance was lower in females, systemic clearance might not be the cause of the different exposures to zolpidem.

Dimeric ferrochelatase bridges ABCB7 and ABCB10 homodimers in an architecturally defined molecular complex required for heme biosynthesis.

Loss-of-function mutations in the ATP-binding cassette (ABC) transporter of the inner mitochondrial membrane, ABCB7, cause X-linked sideroblastic anemia with ataxia, a phenotype that remains largely unexplained by the proposed role of ABCB7 in exporting a special sulfur species for use in cytosolic iron-sulfur (Fe-S) cluster biogenesis. Here, we generated inducible ABCB7-knockdown cell lines to examine the time-dependent consequences of loss of ABCB7. We found that knockdown of ABCB7 led to significant loss of mitochondrial Fe-S proteins, which preceded the development of milder defects in cytosolic Fe-S enzymes. In erythroid cells, loss of ABCB7 altered cellular iron distribution and caused mitochondrial iron overload due to activation of iron regulatory proteins 1 and 2 in the cytosol and to upregulation of the mitochondrial iron importer, mitoferrin-1. Despite the exceptionally large amount of iron imported into mitochondria, erythroid cells lacking ABCB7 showed a profound hemoglobinization defect and underwent apoptosis triggered by oxidative stress. In ABCB7-depleted cells, defective heme biosynthesis resulted from translational repression of ALAS2 by iron regulatory proteins and from decreased stability of the terminal enzyme ferrochelatase. By combining chemical crosslinking, tandem mass spectrometry and mutational analyses, we characterized a complex formed of ferrochelatase, ABCB7 and ABCB10, and mapped the interfaces of interactions of its components. A dimeric ferrochelatase physically bridged ABCB7 and ABCB10 homodimers by binding near the nucleotide-binding domains of each ABC transporter. Our studies not only underscore the importance of ABCB7 for mitochondrial Fe-S biogenesis and iron homeostasis, but also provide the biochemical characterization of a multiprotein complex required for heme biosynthesis.

Quantitative Modeling Analysis Demonstrates the Impact of CYP2C19 and CYP2D6 Genetic Polymorphisms on the Pharmacokinetics of Amitriptyline and Its Metabolite, Nortriptyline.

Amitriptyline is a tricyclic antidepressant that is metabolized mainly by CYP2C19 and CYP2D6 enzymes. Higher plasma levels of amitriptyline and its active metabolite, nortriptyline, are associated with an increased risk of adverse events including anticholinergic effects. The aim of this study was to evaluate the effects of CYP2C19 and CYP2D6 genetic polymorphisms on amitriptyline and nortriptyline pharmacokinetics. Twenty-four Korean healthy adult male volunteers were enrolled in the study after stratification by their CYP2C19 and CYP2D6 genotypes. Serial blood draws for pharmacokinetic analysis were made after a single oral 25-mg dose of amitriptyline was administered. Plasma amitriptyline and nortriptyline concentrations were measured by a validated liquid chromatography with tandem mass spectrometry. Population pharmacokinetic modeling analysis was conducted using NONMEM, which evaluated the effects of CYP2C19 and CYP2D6 genotypes on amitriptyline and nortriptyline pharmacokinetics. The biotransformation of amitriptyline into nortriptyline was significantly different between subjects with the CYP2C19*2/*2, *2/*3, and *3/*3 genotypes and those with the other genotypes, with an estimated metabolic clearance of 17 and 61.5 L/h, respectively. Clearance of amitriptyline through pathways other than biotransformation into nortriptyline was estimated as 18.8 and 30.6 L/h for subjects with the CYP2D6*10/*10 and *10/*5 genotypes and those with the other genotypes, respectively. This study demonstrated a quantitative effect of the CYP2C19 and CYP2D6 genotypes on amitriptyline and nortriptyline pharmacokinetics. Production of nortriptyline from amitriptyline was associated with CYP2C19 genotypes, and clearance of amitriptyline through pathways other than biotransformation into nortriptyline was associated with CYP2D6 genotypes. These observations may be useful in developing individualized, optimal therapy with amitriptyline.

Infused wild-type macrophages reside and self-renew in the liver to rescue the hemolysis and anemia of Hmox1-deficient mice.

Heme oxygenase 1 (HMOX1), the inducible enzyme that catabolizes the degradation of heme into biliverdin, iron, and carbon monoxide, plays an essential role in the clearance of senescent and damaged red blood cells, systemic iron homeostasis, erythropoiesis, vascular hemostasis, and oxidative and inflammatory stress responses. In humans, HMOX1 deficiency causes a rare and lethal disease, characterized by severe anemia, intravascular hemolysis, as well as vascular and tissue damage. Hmox1 knockout (KO) mice recapitulated the phenotypes of HMOX1-deficiency patients and could be rescued by bone marrow (BM) transplantation that engrafted donor's hematopoietic stem cells into the recipient animals after myeloablation. To find better therapy and elucidate the contribution of macrophages to the pathogenesis of HMOX1-deficiency disease, we infused wild-type (WT) macrophages into Hmox1 KO mice. Results showed that WT macrophages engrafted and proliferated in the livers of Hmox1 KO mice, which corrected the microcytic anemia, rescued the intravascular hemolysis, restored iron homeostasis, eliminated kidney iron overload and tissue damage, and provided long-term protection. These results showed that a single macrophage infusion delivered a long-term curative effect in Hmox1 KO mice, obviating the need for BM transplantation, and suggested that the HMOX1 disease stems mainly from the loss of viable reticuloendothelial macrophages. Our work provides new insights into the etiology of HMOX1 deficiency and demonstrates the potential of infusion of WT macrophages to prevent disease in patients with HMOX1 deficiency and potentially other macrophage-related diseases.

Cytosolic HSC20 integrates de novo iron-sulfur cluster biogenesis with the CIAO1-mediated transfer to recipients.

Iron-sulfur (Fe-S) clusters are cofactors in hundreds of proteins involved in multiple cellular processes, including mitochondrial respiration, the maintenance of genome stability, ribosome biogenesis and translation. Fe-S cluster biogenesis is performed by multiple enzymes that are highly conserved throughout evolution, and mutations in numerous biogenesis factors are now recognized to cause a wide range of previously uncategorized rare human diseases. Recently, a complex formed of components of the cytoplasmic Fe-S cluster assembly (CIA) machinery, consisting of CIAO1, FAM96B and MMS19, was found to deliver Fe-S clusters to a subset of proteins involved in DNA metabolism, but it was unclear how this complex acquired its fully synthesized Fe-S clusters, because Fe-S clusters have been alleged to be assembled de novo solely in the mitochondrial matrix. Here, we investigated the potential role of the human cochaperone HSC20 in cytosolic Fe-S assembly and found that HSC20 assists Fe-S cluster delivery to cytosolic and nuclear Fe-S proteins. Cytosolic HSC20 (C-HSC20) mediated complex formation between components of the cytosolic Fe-S biogenesis pathway (ISC), including the primary scaffold, ISCU1, and the cysteine desulfurase, NFS1, and the CIA targeting complex, consisting of CIAO1, FAM96B and MMS19, to facilitate Fe-S cluster insertion into cytoplasmic and nuclear Fe-S recipients. Thus, C-HSC20 integrates initial Fe-S biosynthesis with the transfer activities of the CIA targeting system. Our studies demonstrate that a novel cytosolic pathway functions in parallel to the mitochondrial ISC to perform de novo Fe-S biogenesis, and to escort Fe-S clusters to cytoplasmic and nuclear proteins.

A Single Adaptable Cochaperone-Scaffold Complex Delivers Nascent Iron-Sulfur Clusters to Mammalian Respiratory Chain Complexes I-III.

The iron-sulfur (Fe-S) cluster of the Rieske protein, UQCRFS1, is essential for Complex III (CIII) activity, though the mechanism for Fe-S cluster transfer has not previously been elucidated. Recent studies have shown that the co-chaperone HSC20, essential for Fe-S cluster biogenesis of SDHB, directly binds LYRM7, formerly described as a chaperone that stabilizes UQCRFS1 prior to its insertion into CIII. Here we report that a transient subcomplex involved in CIII assembly, composed of LYRM7 bound to UQCRFS1, interacts with components of an Fe-S transfer complex, consisting of HSC20, its cognate chaperone HSPA9, and the holo-scaffold ISCU. Binding of HSC20 to the LYR motif of LYRM7 in a pre-assembled UQCRFS1-LYRM7 intermediate in the mitochondrial matrix facilitates Fe-S cluster transfer to UQCRFS1. The five Fe-S cluster subunits of Complex I also interact with HSC20 to acquire their clusters, highlighting the crucial role of HSC20 in the assembly of the mitochondrial respiratory chain.

Resurgence of measles in a country of elimination: interim assessment and current control measures in the Republic of Korea in early 2014.

Since the beginning of 2014, the Republic of Korea has experienced a resurgence of measles cases. Among the 220 cases confirmed as measles during epidemiological weeks 1-20 (December 29, 2013 to May 17, 2014), 10 imported cases were identified. The predominant genotype was B3, which reflects the circulating measles virus in adjacent countries. Even with the verification of measles elimination in March 2014 by the World Health Organization, recent importation has been related to international travel. Targeted control measures have been implemented in addition to proper isolation and patient care. A vigilant surveillance system and high levels of vaccine coverage should be maintained to sustain the measles elimination status.

A synthetic model of human beta-thalassemia erythropoiesis using CD34+ cells from healthy adult donors.

Based upon the lack of clinical samples available for research in many laboratories worldwide, a significant gap exists between basic and clinical studies of beta-thalassemia major. To bridge this gap, we developed an artificially engineered model for human beta thalassemia by knocking down beta-globin gene and protein expression in cultured CD34+ cells obtained from healthy adults. Lentiviral-mediated transduction of beta-globin shRNA (beta-KD) caused imbalanced globin chain production. Beta-globin mRNA was reduced by 90% compared to controls, while alpha-globin mRNA levels were maintained. HPLC analyses revealed a 96% reduction in HbA with only a minor increase in HbF. During the terminal phases of differentiation (culture days 14-21), beta-KD cells demonstrated increased levels of insoluble alpha-globin, as well as activated caspase-3. The majority of the beta-KD cells underwent apoptosis around the polychromatophilic stage of maturation. GDF15, a marker of ineffective erythropoiesis in humans with thalassemia, was significantly increased in the culture supernatants from the beta-KD cells. Knockdown of beta-globin expression in cultured primary human erythroblasts provides a robust ex vivo model for beta-thalassemia.

LIN28B-mediated expression of fetal hemoglobin and production of fetal-like erythrocytes from adult human erythroblasts ex vivo.

Reactivation of fetal hemoglobin (HbF) holds therapeutic potential for sickle cell disease and ß-thalassemias. In human erythroid cells and hematopoietic organs, LIN28B and its targeted let-7 microRNA family, demonstrate regulated expression during the fetal-to-adult developmental transition. To explore the effects of LIN28B in human erythroid cell development, lentiviral transduction was used to knockdown LIN28B expression in erythroblasts cultured from human umbilical cord CD34+ cells. The subsequent reduction in LIN28B expression caused increased expression of let-7 and significantly reduced HbF expression. Conversely, LIN28B overexpression in cultured adult erythroblasts reduced the expression of let-7 and significantly increased HbF expression. Cellular maturation was maintained including enucleation. LIN28B expression in adult erythroblasts increased the expression of γ-globin, and the HbF content of the cells rose to levels >30% of their hemoglobin. Expression of carbonic anhydrase I, glucosaminyl (N-acetyl) transferase 2, and miR-96 (three additional genes marking the transition from fetal-to-adult erythropoiesis) were reduced by LIN28B expression. The transcription factor BCL11A, a well-characterized repressor of γ-globin expression, was significantly down-regulated. Independent of LIN28B, experimental suppression of let-7 also reduced BCL11A expression and significantly increased HbF expression. LIN28B expression regulates HbF levels and causes adult human erythroblasts to differentiate with a more fetal-like phenotype.

Regulation of cytosolic phospholipase A2 phosphorylation by proteolytic cleavage of annexin A1 in activated mast cells.

Annexin A1 (ANXA1) is cleaved at the N terminal in some activated cells, such as macrophages, neutrophils, and epithelial cells. We previously observed that ANXA1 was proteolytically cleaved in lung extracts prepared from a murine OVA-induced asthma model. However, the cleavage and regulatory mechanisms of ANXA1 in the allergic response remain unclear. In this study, we found that ANXA1 was cleaved in both Ag-induced activated rat basophilic leukemia 2H3 (RBL-2H3) cells and bone marrow-derived mast cells. This cleavage event was inhibited when intracellular Ca(2+) signaling was blocked. ANXA1-knockdown RBL-2H3 cells produced a greater amount of eicosanoids with simultaneous upregulation of cytosolic phospholipase A(2) (cPLA(2)) activity. However, there were no changes in degranulation activity or cytokine production in the knockdown cells. We also found that cPLA(2) interacted with either full-length or cleaved ANXA1 in activated mast cells. cPLA(2) mainly interacted with full-length ANXA1 in the cytosol and cleaved ANXA1 in the membrane fraction. In addition, introduction of a cleavage-resistant ANXA1 mutant had inhibitory effects on both the phosphorylation of cPLA(2) and release of eicosanoids during the activation of RBL-2H3 cells and bone marrow-derived mast cells. These data suggest that cleavage of ANXA1 causes proinflammatory reactions by increasing the phosphorylation of cPLA(2) and production of eicosanoids during mast-cell activation.

Factors associated with sleep duration in Korean adults: results of a 2008 community health survey in Gwangju metropolitan city, Korea.

Short (≤ 6 hr) and long (≥ 9 hr) sleep durations are both associated with risk factors for cardiovascular diseases and diabetes, depression, learning problems, accidents and excess mortality. However, little is known about factors associated with sleep duration in Korean adults. This study examined sleep patterns in Korean adults and identified factors associated with short and long sleep durations. This study analyzed cross-sectional data collected from 4,411 Korean adults aged 19 yr and older who participated in a community health survey conducted in Gwangju, Korea. Multinomial logistic regression analysis was used to identify associations between socio-demographic and health-related factors and short or long sleep durations. Of the population, 37.2% and 4.0% reported short and long sleep, respectively. Short sleep was associated with older age, lower levels of income, night or shift work, heavy smoking, and depression or anxiety; long sleep was associated with younger age, being divorced or widowed, heavy smoking, underweight, depression or anxiety, and poorer self-reported health. In conclusion, a relatively high prevalence of short sleep duration is identified in this population of Korean adults. Factors associated with short or long sleep may act as potential confounders of the relationship between sleep duration and health outcomes.

14-3-3 η inhibits chondrogenic differentiation of ATDC5 cell.

It was previously shown that 14-3-3 η is overexpressed in the synovial fluid of patients with joint inflammation, which is often associated with growth failure. In this study, we investigated the role of 14-3-3 η in chondrogenesis using ATDC5 cells. Upon treatment with TNF-α, cells overexpressed 14-3-3 η with inhibition of chondrogenesis. Chondrogenesis was also inhibited by overexpression of 14-3-3 η without TNF-α treatment, whereas silencing of 14-3-3 η promoted chondrogenic differentiation. Further, G1 phase arrest was inhibited by overexpression of 14-3-3 η. In summary, we suggest that 14-3-3 η plays a regulatory role in chondrogenic differentiation.

Association between alcohol consumption and bone strength in Korean adults: the Korean Genomic Rural Cohort Study.

Previous studies have reported an inconsistent relationship between alcohol consumption and bone health. A growing body of research has shown that chronic alcoholism leads to osteopenia and increased incidence of skeletal fractures, but some studies have concluded that alcohol consumption may be associated with higher bone mineral density in elderly populations. However, most studies showing a significant relationship between alcohol consumption and bone status have been in Western countries; and subjects have usually been postmenopausal women. The purpose of the present study was to investigate the association of alcohol consumption with bone strength in Korean adults. Data were from the Korean Genomic Rural Cohort Study, which is an ongoing population-based study of adults aged 40 to 70 years from 5 regions. A total of 7713 participants (3368 men, 4345 women) were surveyed about their annual consumption of alcohol such as soju, beer, makkolli, wine, and whisky. Bone strength was measured by stiffness index using the calcaneal quantitative ultrasound method. Overall, the annual age-specific decrease rate in the stiffness index of women was 2.7 times higher than that of men (0.463% for women, 0.169% for men).After adjustment for eligible covariates, the association between alcohol consumption and risk of reduced bone strength showed a J-shaped curve for both men and women. Compared with nondrinkers, the relative risk of reduced bone strength was 0.52 (95% confidence interval, 0.33-0.83) in men who drank 4 to 5 cups of soju for an amount of 29.626 to 49.375 g of alcohol per day and 0.61 (95% confidence interval, 0.38-0.86) in men who drank 6 to 7 cups of soju for an amount of 49.376 to 69.125 g of alcohol per day. We found no significant relationship between alcohol consumption and bone strength in any other group of men. For women, results suggested that the risk of reduced bone strength was lower in the moderate-consumption group; but no significant relationship was found between alcohol consumption at any level and bone strength. Among Korean adults, alcohol consumption has a J-shaped relationship with risk of reduced bone strength.

Oseltamivir-resistant pandemic (H1N1) 2009 virus, South Korea.

To identify oseltamivir resistance, we analyzed neuraminidase H275Y mutations in samples from 10 patients infected with pandemic (H1N1) 2009 virus in South Korea who had influenza that was refractory to antiviral treatment with this drug. A neuraminidase I117M mutation that might influence oseltamivir susceptibility was detected in sequential specimens from 1 patient.

Reactive oxygen species generated by NADPH oxidase 2 and 4 are required for chondrogenic differentiation.

Although generation of reactive oxygen species (ROS) by NADPH oxidases (Nox) is thought to be important for signal transduction in nonphagocytic cells, little is known of the role ROS plays in chondrogenesis. We therefore examined the possible contribution of ROS generation to chondrogenesis using both ATDC5 cells and primary chondrocytes derived from mouse embryos. The intracellular level of ROS was increased during the differentiation process, which was then blocked by treatment with the ROS scavenger N-acetylcysteine. Expression of Nox1 and Nox2 was increased upon differentiation of ATDC5 cells and primary mouse chondrocytes, whereas that of Nox4, which was relatively high initially, was decreased gradually during chondrogenesis. In developing limb, Nox1 and Nox2 were highly expressed in prehypertrophic and hypertrophic chondrocytes. However, Nox4 was highly expressed in proliferating chondrocytes and prehypertrophic chondrocytes. Depletion of Nox2 or Nox4 expression by RNA interference blocked both ROS generation and differentiation of ATDC5 cells, whereas depletion of Nox1 had no such effect. We also found that ATDC5 cells depleted of Nox2 or Nox4 underwent apoptosis. Further, inhibition of Akt phosphorylation along with subsequent activation of ERK was observed in the cells. Finally, depletion of Nox2 or Nox4 inhibited the accumulation of proteoglycan in primary chondrocytes. Taken together, our data suggest that ROS generated by Nox2 or Nox4 are essential for survival and differentiation in the early stage of chondrogenesis.

[Associated factors of impaired fasting glucose in some Korean rural adults].

OBJECTIVES: This study was performed to investigate the prevalence of impaired fasting glucose (IFG) and its related characteristics among healthy adults in some Korean rural areas. METHODS: We conducted a cross-sectional study using the data from 1352 adults who were over the age 40 and under the age 70 and who were free of diabetes mellitus (DM), cardiovascular diseases and other diseases and who participated in a survey conducted as part of the Korean Rural Genomic Cohort Study. IFG was defined as a serum fasting glucose level between 100 and 125 mg/dL. RESULTS: The prevalence of IFG was 20.4% in men, 15.5% in women and 12.7% overall. Multivariate logistic regression analysis demonstrated that the independent risk factors for IFG were male gender, having a family history of DM, the quartiles of gamma glutamyltransferase and high sensitive C-reactive protein and the waist circumference. The homeostatis model assessment for insulin resistance was very strongly associated with IFG. The prevalence of metabolic syndrome (MS) and MS components was higher in the subjects with IFG then in those with normal fasting glucose (NFG). CONCLUSIONS: The result of study could supply evidence to find the high risk population and to determine a strategy for treating IFG. Further research is needed to explain the causal relationship and mechanisms of IFG.

Preliminary report: a serious link between adiponectin levels and metabolic syndrome in a Korean nondiabetic population.

This large-scale cross-sectional investigation highlights the relationships between adiponectin levels and a number of metabolic syndrome components in a nondiabetic Korean population (N = 6634). In a multivariate logistic regression model, after adjustment for age, homeostasis model assessment of insulin resistance, body mass index, smoking history, C-reactive protein, and low-density lipoprotein cholesterol, adiponectin levels were inversely related with metabolic syndrome in men and women (P < .05). Adiponectin level was found to be a significant contributor to metabolic syndrome. Our findings suggest that adiponectin is an important biomarker even in a nondiabetic population at high risk of metabolic syndrome.

Associations between smoking and alcohol drinking and suicidal behavior in Korean adolescents: Korea Youth Behavioral Risk Factor Surveillance, 2006.

OBJECTIVE: To assess any association between cigarette smoking and heavy drinking and suicidal ideation and suicide attempts among boys and girls in a nationally representative sample of Korean adolescents. METHOD: The analysis was performed using data from the 2006 Korea Youth Behavioral Risk Factor Surveillance study, which included a representative sample of middle and high school students in Korea. Logistic regression analyses were conducted to examine whether smoking and drinking were associated with suicidal behavior among boys and girls, controlling for demographic characteristics, perceived stress, perceived sadness/hopelessness, and chronic disease. RESULTS: Of the 70,486 study subjects, 23.3% (19.1% of boys and 27.9% of girls) reported suicidal ideation and 5.3% (4.6% of boys and 6.1% of girls) reported having attempted suicide during the previous 12 months. Cigarette smoking and heavy drinking were found to be significantly associated with suicidal ideation and suicidal attempts among boys and girls. CONCLUSION: Smoking and heavy drinking among adolescents are important factors related to suicidal ideation and attempting suicide in boys and girls. Further research is needed to clarify any causal connection between cigarette smoking and heavy drinking and suicidal ideation and suicide attempts.

Molecular characterization and phylogenetic analysis of H3N2 human influenza A viruses in Cheongju, South Korea.

To investigate the genetic characteristics of human influenza viruses circulating in Chungbuk province, we tested 510 clinical samples of nasopharyngeal suction from pediatric patients diagnosed with respiratory illness between June 2007 and June 2008. Genetic characterization of the HA genes of H3N2 isolates indicated the relative higher similarity to A/Virginia/04/07 (99.6%) rather than that of A/Wisconsin/67/2005 (98.4%), a Northern Hemisphere 2007-2008 vaccine strain, based on amino acid sequences. We found several altered amino acids at the H3 HA1 antigenic sites compared with the vaccine strain; K140I at site A, K158R at site B, and K173N (H471) or K173Q, and S262N at site E, but there was no antigenic shift among the H3N2 viruses. Interestingly, A/Cheongju/H383/08 and A/Cheongju/H407/08 isolates had single amino acid substitution at D151G on the catalytic site of the N2 NA while A/Cheongju/H412/08 and A/Cheongju/ H398/07 isolates had one amino acid deletion at residue 146. Furthermore, we found that 25% (3 out of 12 isolates) of the H3N2 subtype viruses had the amino acid substitution at position 31 on the M2 protein (Aspartic acid to Asparagine) and confirmed their drug-resistance by biological assays. Taken together, the results of this study demonstrated continuous evolutions of human H3N2 viruses by antigenic drift and also highlighted the need to closely monitor antigenic drug resistance in influenza A viruses to aid in the early detection of potentially pandemic strains, as well as underscore the need for new therapeutics.

The association between circulating inflammatory markers and metabolic syndrome in Korean rural adults.

OBJECTIVES: This study was performed to investigate the associations between the metabolic syndrome (MetS) and inflammatory markers. METHODS: This cross-sectional analysis was performed using data from 1578 Koreans aged 40-69 years residing in a rural area. We investigated associations between MetS and circulating high sensitivity C-reactive protein (hs-CRP), white blood cells (WBC) and adiponectin. MetS was defined using the criteria proposed by the National Cholesterol Education Program Adult Treatment Panel III (ATP-III). RESULTS: Increased WBC counts and hs-CRP levels and decreased adiponectin levels were observed in subjects with MetS. WBC, hs-CRP and adiponectin levels linearly deteriorated with an increase in the number of MetS components (all ptrend <0.005). Finally, adjusted odds ratios (ORs) for the risk of MetS by increase/decrease in 3 inflammatory markers were calculated by multivariate logistic regression analyses. In terms of changes in inflammation markers, in men, the adjusted ORs (95% confidence interval) were 1.15 (1.01-1.31) for WBC, 1.64 (1.02-2.64) for hs-CRP, and 0.19 (0.08-0.45) for adiponectin, whereas corresponding adjusted ORs (95% CIs) in women were 1.27 (1.15-1.40), 0.98 (0.67-1.42), 0.09 (0.04-0.18), respectively. CONCLUSIONS: Serum adiponectin levels and WBC counts were found to be strongly associated with MetS in both sexes. However, hs-CRP lost its significance after adjusting for BMI and other inflammatory markers in women. This study shows that inflammatory response is associated with MetS in the Korean population. Further prospective studies are necessary to confirm the contribution made by inflammatory markers to the development of MetS.