The Effects of Phlomis umbrosa Turcz on Osteoclast Differentiation / 체질인류학회지

Many bone-related diseases such as osteoporosis, rheumatoid arthritis are occurred by excessive bone resorbing activity of osteoclasts. Recently, many studies have been proceeded to find out the new therapeutic materials from natural products of plants. Phlomis umbrosa Turcz, one of the natural products of plants has been known to improve bone health. However, the precise effects and treatment mechanisms of Phlomis umbrosa Turcz about bone diseases has been unknown. So, we examined the effects of Phlomis umbrosa Turcz on expression of receptor activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclast differentiation in bone marrow-derived macrophages (BMMs) and bone resorption. Also, we investigated the treatment mechanisms of Phlomis umbrosa Turcz relating to osteoclast differentiation. Here, we showed that Phlomis umbrosa Turcz significantly suppressed RANKL-induced osteoclast differentiation and bone resportion. Furthermore, Phlomis umbrosa Turcz suppressed the activation of NF-kappaB in bone marrow macrophage treated RANKL and M-CSF. The mRNA expression of c-Fos, nuclear factor of activated T-cells (NFAT)c1, osteoclast-associated receptor (OSCAR), tartrate-resistant acid phosphatase (TRAP) in BMMs was inhibited by Phlomis umbrosa Turcz. Integrin alphanu, beta3 relating to cell adhesion and dendritic cell-specific transmembrane protein (DC-STAMP) relating to the structure of filamentous actin (F-actin) ring and cathepsin K relating to bone resorbing activity are disrupted too. These results suggest that Phlomis umbrosa Turcz will be a good materials to treat bone diseases like osteoporosis.

Effect of Cornus Officinalis on Receptor Activator of Nuclear Factor-kappaB Ligand (RANKL)-induced Osteoclast Differentiation

OBJECTIVES: Osteoporosis is a disease of bones that is thought to result from an imbalance between bone resorption and bone formation. Although osteoporosis itself has no symptoms, osteoporosis caused by osteoclasts leads to an increased risk of fracture. Here we examined the effects of cornus officinalis on receptor activator of nuclear factor-kappaB ligand (RANKL)-mediated osteoclast differentiation. METHODS: We evaluated the effects of cornus officinalis on RANKL-induced osteoclast differentiation from bone marrow-derived macrophages (BMMs) and performed a cytotoxicity assay, reverse transcriptase-polymerase chain reaction (RT-PCR), and Western blot analysis. RESULTS: Cornus officinalis significantly inhibits RANKL-mediated osteoclast differentiation in a dose-dependent manner, but without cytotoxicity against BMMs. The mRNA expression of tartrate-resistant acid phosphatase (TRAP), osteoclast-associated receptor (OSCAR), c-Fos, and nuclear factor of activated T cells cytoplasmic 1 (NFATc1) in BMMs treated with RANKL was considerably inhibited by cornus officinalis treatment. Also, cornus officinalis inhibits the protein expression of c-Fos and NFATc1. Cornus officinalis greatly inhibits RANKL-induced phosphorylation of p38 and c-JUN N-terminal kinase (JNK). Also, cornus officinalis significantly suppresses RANKL-induced degradation of I-kappaB. CONCLUSIONS: Taken together, our results suggest that cornus officinalis may be a useful the treatment of osteoporosis.

Inhibition of Osteoclast Differentiation and Bone Resorption by Poria cocos Wolf Extract / 대한골다공증학회지

OBJECTIVES: Osteoclast differentiation and bone resorption are considered a potential therapeutic target to the treatment of erosive bone diseases, including osteoporosis and rheumatoid arthritis. Poria cocos Wolf (PCW), commonly used herbal medicine, has previously been reported to induce anti-inflammatory effect and anti-cancer effect, and to modulate immunologic responses. However, the effects of PCW on osteoclasts, and its detailed mechanisms are not proven. Therefore, we examined the inhibitory mechanism of PCW on osteoclast differentiation and bone resorption. MATERIALS AND METHODS: To analyze the effects of PCW on osteoclast differentiation, we examined osteoclast differentiation in bone marrow macrophages (BMMs) treated with or without of PCW by TRAP staining. The expression of c-Fos, NFATc1, TRAP and OSCAR mRNA was determined by RT-PCR and the protein levels of c-Fos, NFATc1, p38, ERK, JNK, Akt and IkappaB were assessed by western blot. Also, we evaluated the effect of PCW on bone resorption using hydroxyapatite plate. RESULTS: PCW significantly inhibited RANKL-mediated osteoclast differentiation without any evidence of cytotoxicity. We founded that PCW strongly inhibited RANKL-induced osteoclast formation when added during the early stage of cultures, suggesting that PCW acts on osteoclast precursors to inhibit RANKL/RANK signaling. Among the RANK signaling pathways, PCW inhibited the phosphorylation of p38 and JNK, also inhibited RANKL-induced expression of c-Fos, NFATc1, TRAP and OSCAR. In addition, PCW suppressed the bone resorption of mature osteoclasts. CONCLUSIONS: These findings suggest that PCW may be a potential novel drug for bone disorders by targeting the differentiation of osteoclasts as well as their functions.

Inhibitory Effects of 1',2'-Dihydrorotenone on Osteoclast Differentiation and Bone Resorption In Vitro and In Vivo / 체질인류학회지

It is important to identify therapeutic compounds with no adverse effects for use in the chemotherapy of patients with bone-related diseases. The aim of this study was to identify a new compound that inhibits osteoclast differentiation and bone resorption. Herein, we examined the effects of 1',2'-dihydrorotenone on osteoclast differentiation and bone resorption in vitro and in vivo. 1',2'-dihydrorotenone inhibited receptor activator of NF-kappaB ligand (RANKL)-induced osteoclast differentiation of cultured bone marrow macrophages (BMMs) in a dose-dependent manner. However, 1',2'-dihydrorotenone did not exert cytotoxic effect on BMMs. 1',2'-dihydrorotenone suppressed the expression of c-fos and NFATc1 as well as osteoclast-specific genes in BMMs treated with RANKL. Treatment with RANKL inhibited the expression of inhibitors of differentiation/DNA binding (Id)1, 2, and 3; however, in the presence of 1',2'-dihydrorotenone, RANKL did not suppress the expression of Id1, 2, and 3. Furthermore, 1',2'-dihydrorotenone inhibited bone resorption and considerably attenuated the erosion of trabecular bone induced by lipopolysaccharide treatment. Taken together, these results suggest that 1',2'-dihydrorotenone has the potential to be applied in therapies for bone-related diseases.

Amorphigenin inhibits Osteoclast differentiation by suppressing c-Fos and nuclear factor of activated T cells / 대한해부학회지

Among the several rotenoids, amorphigenin is isolated from the leaves of Amopha Fruticosa and it is known that has anti-proliferative effects and anti-cnacer effects in many cell types. The main aim of this study was to investigate the effects of amorphigenin on osteoclast differentiation in vitro and on LPS treated inflammatory bone loss model in vivo. We show here that amorphigenin inhibited RANKL-induced osteoclast differentiation from bone marrow macrophages in a dose dependent manner without cellular toxicity. Anti-osteoclastogenic properties of amorphigenin were based on a down-regulation of c-fos and NFATc1. Amorphigenin markedly inhibited RANKL-induced p38 and NF-kappaB pathways, but other pathways were not affected. Micro-CT analysis of the femurs showed that amorphigenin protected the LPS-induced bone loss. We concluded that amorphigenin can prevent inflammation-induced bone loss. Thus we expect that amorphigenin could be a treatment option for bone erosion caused by inflammation.

Effect of Water Extract of Papaya on RANKL-induced Osteoclast Differentiation / 대한해부학회지

Balance between bone-resorbing osteoclats and bone-forming osteoblasts is important in bone homeostasis. In particular, increased osteoclast formation and activity are responsible for bone diseases such as osteoporosis, rheumatoid arthritis, periodontal disease. Natural metabolites of plants have recently received much attention as lead compounds for the development of novel therapeutic strategy. The purpose of this study was to search the natural products to inhibition osteoclast differentiation. Water extract of papaya significantly inhibited receptor activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclast differentiation in bone marrow macrophages (BMMs) in a dose dependent manner. However, water extract of papaya did not affect cytotoxicity when compared with control. Water extract of papaya inhibited the phosphorylation of p38 and JNK induced by RANKL. The mRNA expression of c-Fos, NFATcl, TRAP and OSCAR induced by RANKL was inhibited by water extract of papaya treatment. Also, water extract of papaya suppressed the protein expression of c-Fos and NFATc1 in BMMs treated with RANKL. Taken together, these results suggest that papaya may be a useful drug in the treatment of bone-related disease.

Effect of Jak2 Inhibitor AG490 on Osteoclast Differentiation / 대한해부학회지

Osteoclasts are cells of hemopoietic origin that play an critical role in bone resorption and responsible for bone diseases, including osteoporosis, periodontal disease, and rheumatoid arthritis. In this study, we examined the effect of AG490, a Jak2-specific inhibitor on osteoclast differentiation. AG490 significantly inhibited receptor activator of NF-kappaB ligand (RANKL)-mediated osteoclast differentiation in a dose-dependent manner. RANKL stimulated the phosphorylation of p38, ERK, and JNK and promoted I-kappaB degradation. However, AG490 suppressed the phosphorylation of p38 induced by RANKL treatment. AG490 suppressed the mRNA expression of TRAP, c-Fos, NFATc1, and OSCAR in bone marrow-derived macrophages (BMMs) treated with RANKL. Also, AG490 significantly inhibited the protein expression of c-Fos and NFATc1 in response to RANKL. These results suggest that AG490 inhibited osteoclast differentiation by suppressing the expression of c-Fos and NFATc1.

Roles of Sphingosine-1 Phosaphate During Pathogenesis of Bone Destruction and Inflammation in Rheumatoid Arthritis Mice Model / 대한해부학회지

Sphingosine 1-phosphate (S1P) is a bioactive lipid molecule that mediates cell proliferation, differentiation, migration, and angiogenesis in vivo. However, the roles of S1P on pathogenesis of arthritis have been not completely understood. This study was designed to determine the effects of S1P modulation on collageninduced arthritis (CIA) model. DBA/1J mice were injected with collagen into the tail for induction of CIA model. S1P was administered into the peritoneal cavity every other days from day 1 to day 42 after collagen injection. To determine the degree of damage in CIA, we examined macroscopic findings of CIA. The inflammation and bone destruction of CIA mice were evaluated by histo-patholigy and radiography (CT and microradiography). The expressions of TNF-alpha, IL-6, and RANKL which have important roles in pathogenesis of rheumatoid arthritis and bone destruction were observed by immuno-histochemical staining. After injection with collagen in the DBA/1J mice, CIA was induced by swelling in the knee and ankle joint. Administration of S1P suppressed damages and incidence of arthritis elicited by collagen. In histologic and radiographic studies, S1P strongly suppressed the infiltration of inflammatory cells, the swelling of synovial membrane, erosion, and the destruction of bone on CIA mice. Injection of S1P resulted in down-regulation of the expression of the pro-inflammatory and bone destruction mediators such as TNF-alpha, IL-6, and RANKL on CIA mice. Furthermore, S1P suppressed the differentiation of bone marrow cells into osteoclasts by RANKL. In conclusion, this study suggest that S1P has protective effects on inflammation and bone destruction during pathogenesis of CIA, which indicates S1P can be a new possible therapeutic strategy for rheumatoid arthritis

A Study of Susceptibility between Allergic Rhinitis and Tumor Necrosis Factor Gene Polymorphism Study in Korean / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Tumor necrosis factor-alpha (TNF-alpha) is recognized as a proinflammatory host alert cytokine that is synthesized early during inflammation, and elevations of this cytokine have been reported in patients with allergic rhinitis. The TNF-alpha gene is located on chromosome 6p within the class III region of the major histocompatibility complex. The most widely studied polymorphism within the TNF-alpha gene involves a guanine (G)/adenine (A) substitution at position -308. We therefore tested whether TNF-alpha -308G/A polymorphism are associated with allergic rhinitis in a Korean population. SUBJECTS AND METHOD: Blood samples for genetic analysis were obtained from 191 individuals with allergic rhinitis and from 192 healthy subjects without atopic diseases. Polymerase chain reaction-based assay for TNF-alpha -308G/A was used for genotyping. Serum total IgE levels were determined by using the immunoassay. Eosinophil values were determined by eosinophil numbers per total cell numbers per microliter. RESULTS: There were no differences in the frequencies of the genotypes and alleles of TNF-alpha -308G/A in the controls and patients(p>0.05). Blood eosinophil count and total serum IgE levels were not statistically different in the genotypes of TNF-alpha -308G/A in allergic rhinitis(p>0.05). CONCLUSION: We thought that the TNF-alpha -308G/A polymorphism is unlikely to be an important marker for predisposition to allergic rhinitis. A further study involving a larger Korean population might be in need.

A Study of Susceptibility between Allergic Rhinitis and FcepsilonRIbeta Gene Polymorphism Study in Korean / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Human basophils and mast cells play a central role in allergic disease. The beta subunit of the high affinity IgE receptor (FcepsilonRIbeta) gene is one of the candidate genes for atopy because of its important role in initiating type I allergic reaction in mast cells and basophils. We therefore tested whether Gly237Glu variants of FcepsilonRIbeta are associated with atopy in the Korean population. SUBJECTS AND METHOD: Blood samples for genetic analysis were obtained from 175 individuals with allergic rhinitis and from 191 healthy subjects without atopic diseases. Polymerase chain reaction-based assay for FcepsilonRIbeta Glu237Gly was used for genotyping. Serum total IgE levels were determined by using the immunoassay. Eosinophil values were determined by eosinophil numbers per total cell numbers per microliteriter. RESULTS: There were no differences in the frequencies of the genotypes and alleles of FcepsilonRIbeta between the controls and patients (p>0.05). Blood eosinophil count and total serum IgE levels were not statistically different in the genotypes of FcepsilonRIbeta in allergic rhinitis (p>0.05). Although statistical significance of genotypes of FcepsilonRIbeta was not observed with respect to gender in allergic rhinitis (p=0.057), mutant genotype was two times more prevalent in male patients than in female patients. CONCLUSION: Our results suggest the FcepsilonRIbeta Glu237Gly polymorphism does not affect the susceptibility of Koreans to allergic rhinitis. But our finding indicates that, males as opposed to females, might be predisposed to have the mutant genotype.

A Study of Susceptibility between Allergic Rhinitis and Glutathione S-Transferase Gene Polymorphism Study in Korean / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Glutathione S-transferase (GST) enzymes have an important role in preventing the build-up of reactive oxygen species. Polymorphisms in genes involved in response to oxidative stress may play a role in the susceptibility to allergic diseases in human. A common homozygous deletion(null type) polymorphism of the GST gene abolishes the antioxidative enzyme activity. We investigated whether the profile of GSTM1 and GSTT1 genotypes might be associated with the risk of allergic rhinitis. SUBJECTS AND METHOD: Blood samples for genetic analysis were obtained from 287 individuals with allergic rhinitis and from 262 healthy subjects without atopic diseases. Multiplex polymerase chain reaction-based assay for GSTM1and GSTT1 was used for genotyping. RESULTS: The null genotype was more frequent in controls and the frequencies of the genotypes of GSTM1 were statistically different between controls and patients (p0.05). CONCLUSION: Our result suggests that the GSTM1 and GSTT1 polymorphism is not associated with the susceptibility to allergic rhinitis in Koreans.

A Study of Susceptibility between Allergic Rhinitis and IL-4 Receptor alpha Gene Polymorphism Study in Korean / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The IL-4 receptor (IL-4R) gene has been suggested as a candidate gene for atopic diseases. The IL-4R consists of two subunits: the alpha chain (IL-4Ralpha), which is a high-affinity IL-4 binding site shared with the IL-13R, and the common gamma chain shared with several other cytokine receptors that amplifies signalling of the alpha chain. A Gln551Arg polymorphism of the IL-4Ralpha gene was shown to be a gain-of-function mutation and was associated with atopy. We tested whether a Gln551Arg polymorphism of IL-4Ralpha gene is associated with allergic rhinitis, blood eosinophil counts and total serum IgE levels in the Korean population. SUBJECTS AND METHOD: Blood samples for genetic analysis were obtained from 192 individuals with allergic rhinitis and from 191 healthy subjects without atopic diseases. Polymerase chain reaction-based assay for IL-4Ralpha Gln551Arg was used for genotyping. Serum total IgE levels were determined by using the immunoassay. Eosinophil values were determined by eosinophil numbers per total cell numbers per microL . RESULTS: There were no differences in the frequencies of the genotypes of IL-4Ralpha in the controls and patients (p>0.05). The frequencies of the IL-4Ralpha Arg551 allele were statistically different between controls and patients (p>0.05). Blood eosinophil count and total serum IgE levels were not statistically different in the genotypes of IL-4Ralpha Gln551Arg in allergic rhinitis (p>0.05). CONCLUSION: Our result suggests that the IL-4Ralpha Gln551Arg polymorphism might not give susceptibility to the development of allergic rhinitis in Koreans.

A Study of Susceptibility between Allergic Rhinitis and IL-13 Exon 4 G2044A Gene Polymorphism Study in Korean / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: High total serum IgE level is one of the characteristics seen in allergic rhinitis. IL-13 provides impetus to immunoglobulin class switching to IgE. The IL-13 promoter single nucleotide polymorphism has been shown to be associated with allergic diseases and abnormal IL-13 production. We tested whether a polymorphism in the coding region of IL-13 gene is associated with allergic rhinitis, blood eosinophil counts and total serum IgE levels in Korean. SUBJECTS AND METHOD: Blood samples for genetic analysis were obtained from 307 individuals with allergic rhinitis and from 268 healthy subjects without atopic diseases. Polymerase chain reaction-based assay for IL-13 exon 4 G2044A was used for genotyping. Serum total IgE levels were determined by using the immunoassay. Eosinophil values were determined by eosinophil numbers per total cell numbers per microl. RESULTS: There were no differences in the frequencies of the genotypes of IL-13 in the controls and patients (p>0.05). The frequencies of the IL-13 exon 4 2044A allele were statistically different between controls and patients (p0.05). CONCLUSION: Our result suggests that the IL-13 exon 4 G2044A polymorphism might give susceptibility to the development of allergic rhinitis in Koreans.

A Study of Prevalence between Allergic Rhinitis and CCR5 Gene Polymorphism Study of a Korean Population / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: CC chemokine receptor (CCR5) is characteristic of the Th 1 phenotype, the receptor of RANTES, MIP-1alphaand MIP-1beta. The receptor of CCR5 delta32 (a 32 bp deletion in the CCR5 gene, mutant type) results in the production of a non-functional receptor. Given the potential importance of CCR5 in allergic inflammation, we hypothesized that individuals carrying the CCR5 delta32 allele would show a reduced prevalence of allergic rhinitis. SUBJECTS AND METHOD: Blood samples for genetic analysis were obtained from 187 individuals with allergic rhinitis and from 278 healthy subjects without atopic diseases. Polymerase chain reaction-based assay for the CCR5 gene polymorphism was used for genotyping. RESULTS: We could not find the CCR5 delta32 homozygotes and heterozygotes at all in neither of the controls nor allergic rhinitis Korean patients. CONCLUSION: Since the CCR5 delta32 allele frequency did not deviate from that in the healthy control population, it is unlikely that this allele influences predisposition to allergic rhinitis in Koreans.

A Study of Susceptibility between Allergic Rhinitis and STAT6 Gene G2964A Polymorphism Study of a Korean Population / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: T helper-type 2 cytokines, such as IL-4 and IL-13, may play a central role in allergic diseases. The proteins known as signal transducers and activators of transcription 6 (STAT-6) are key transcription factors involved in both IL-4 and IL-13 mediated biological responses. Since a polymorphism of STAT6 G2964A has been found, we investigated the association between the polymorphism of STAT6 G2964A and allergic rhinitis in Korean. SUBJECTS AND METHOD: Blood samples for genetic analysis were obtained from 229 individuals with allergic rhinitis and from 278 healthy subjects without atopic diseases. Polymerase chain reaction-based assay for the STAT6 G2964A variant was used for genotyping. RESULTS: There were no differences in the frequencies of the genotypes between the controls and patients (p>0.05). The frequencies of the STAT6 2964A allele were not statistically different between controls and allergic rhinitis patients (p>0.05). CONCLUSION: Our result suggests that the STAT6 G2964A polymorphism might not give susceptibility to the development of allergic rhinitis in Koreans.

STAT6 Gene Polymorphisms in Allergic Rhinitis

T helper-type 2 cytokines, such as IL-4 and IL-13, may play a central role in allergic diseases. The protein known as signal transducers and activators of transcription 6 (STAT6) is a key transcription factor involved in both IL-4- and -13-mediated biological responses. Two polymorphisms of the STAT 6 gene (exon 1 and G2964A variant) have been found. We investigated whether these STAT6 gene polymorphisms were associated with allergic rhinitis. Blood samples for genetic analysis were obtained from 285 individuals with allergic rhinitis and from 271 healthy subjects without atopic disease. The G2964A variant of the STAT6 gene was genotyped using PCR-RFLP analysis. The GT repeat polymorphism in exon 1 of the STAT6 gene was genotyped by fragment analysis. There was no association between the 2964A variant and GT repeat polymorphism in exon 1 of the STAT6 and allergic rhinitis in a Korean population (both p > 0.05). Our results suggest that a combination of STAT6 gene polymorphisms is not a useful marker for predicting allergic rhinitis.

Molecular variations in Th1-specific cell surface gene Tim-3

The family of T-cell immunoglobulin domain and mucin domain (TIM) proteins is identified to be expressed on T cells. A member of Tim family, Tim-3 (T cell immunoglobulin mucin 3) is selectively expressed on the surface of differentiated Th1 cells. Tim-3 might have an important role in the induction of autoimmune diseases by regulating macrophage activation and interacts with Tim-3 ligand to regulate Th1 responses. To determine the variation sites in the coding and promoter region of human Tim-3 gene, we performed variation scanning by direct sequencing using the genomic DNA isolated from the patients with asthma or allergic rhinitis and healthy controls without asthma and allergic rhinitis. We identified four single nucleotide polymorphisms (SNPs) including one novel SNPs (-1541C>T) and two variation sites (-1292_-1289delTAAA and -1282_-1278dupTAAAA) in the coding and promoter region of human Tim-3 gene in both the patients and healthy groups.

Vitamin D Receptor Gene BsaM I Polymorphism as Genetic Marker in Patients with Calcium Stone / 대한비뇨기과학회지

PURPOSE: To identify candidate genes related with urolithiasis, the vitamin D receptor (VDR) gene polymorphisms were searched. MATERIALS AND METHODS: Between July 2002 and June 2003, 212 healthy subjects, used as normal controls, and 155 patients with urolithiasis were examined. The control volunteers had no histories of urolithiasis, familial stone disease or osteoporosis. The patients underwent a stone metabolic study and stone analysis. 49 patients received a stone analysis, of which, 45 had calcium stones. Using a polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) analysis of peripheral blood, the association between the VDR gene BsaM I polymorphism and urolithiasis was evaluated. The polymorphism was divided into three groups: excisable (C/C), unexcisable (T/T) and heterozygote (C/T). RESULTS: For the VDR gene BsaM I polymorphism, there was no statistically difference between the control and the urolithiasis groups. The distribution of VDR genotypes in the 155 patients with urolithiasis was as follows: C/C, 139 (89.7%); C/T, 12 (7.7%) and T/T, 4 (2.6%), which was not significantly different from that in the 212 control subjects: C/C, 195 (92.0%); C/T, 14 (6.6%) and T/T, 3 (1.4%). The frequencies of VDR genotypes in the 45 patients with calcium stone were: C/T (13.3%) and T/T (6.7%), and that of the T allele 13.3%, which were significantly different from those of the controls: C/T (6.6%) and T/T (1.4%) and that of the T allele, 4.7% (p<0.05). CONCLUSIONS: VDR BsaM I polymorphism appears to be a good candidate for a genetic marker in calcium stone disease. The T allele especially may be in charge of the pathogenesis of calcium stones. Further analysis and case accumulation are required to identify the genetic marker of urolithiasis. (Korean J Urol 2004;45:1143-1147)

Vitamin D Receptor Gene BsaM I Polymorphism as Genetic Marker in Patients with Calcium Stone / 대한비뇨기과학회지

PURPOSE: To identify candidate genes related with urolithiasis, the vitamin D receptor (VDR) gene polymorphisms were searched. MATERIALS AND METHODS: Between July 2002 and June 2003, 212 healthy subjects, used as normal controls, and 155 patients with urolithiasis were examined. The control volunteers had no histories of urolithiasis, familial stone disease or osteoporosis. The patients underwent a stone metabolic study and stone analysis. 49 patients received a stone analysis, of which, 45 had calcium stones. Using a polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) analysis of peripheral blood, the association between the VDR gene BsaM I polymorphism and urolithiasis was evaluated. The polymorphism was divided into three groups: excisable (C/C), unexcisable (T/T) and heterozygote (C/T). RESULTS: For the VDR gene BsaM I polymorphism, there was no statistically difference between the control and the urolithiasis groups. The distribution of VDR genotypes in the 155 patients with urolithiasis was as follows: C/C, 139 (89.7%); C/T, 12 (7.7%) and T/T, 4 (2.6%), which was not significantly different from that in the 212 control subjects: C/C, 195 (92.0%); C/T, 14 (6.6%) and T/T, 3 (1.4%). The frequencies of VDR genotypes in the 45 patients with calcium stone were: C/T (13.3%) and T/T (6.7%), and that of the T allele 13.3%, which were significantly different from those of the controls: C/T (6.6%) and T/T (1.4%) and that of the T allele, 4.7% (p<0.05). CONCLUSIONS: VDR BsaM I polymorphism appears to be a good candidate for a genetic marker in calcium stone disease. The T allele especially may be in charge of the pathogenesis of calcium stones. Further analysis and case accumulation are required to identify the genetic marker of urolithiasis. (Korean J Urol 2004;45:1143-1147)

Genetic Susceptibilities of MCP-1 and CCR2 to the Risk for Korean Allergic Rhinitis Patients Using Polymorphism Study / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: A biallelic A/G polymorphism in the Monocyte chemotactic protein (MCP) -1 at position -2518 has been found to affect the level of MCP-1 expression. To investigate if these polymorphisms in chemokine ligand and receptor genes are relevant for the development of allergic rhinitis, we investigated polymorphisms of MCP-1 and CC chemokine receptor 2 (CCR2) known as the receptor of MCP-1. MATERIALS AND METHOD: Blood samples for genetic analysis were obtained from 198 individuals with allergic rhinitis and from 278 healthy subjects without atopic diseases. Polymerase chain reaction-based assay for MCP-1 -2518 A/G (A/G polymorphism in the MCP-1 at position -2518) and CCR2 V64I polymorphisms (replacement of valine by isoleucine in CCR2 64) was used for genotyping. RESULTS: There were no differences in the frequencies of the genotypes in the controls and patients (p>0.05). The frequencies of the MCP-1 G and CCR2 A alleles were not statistically different between controls and allergic rhinitis patients (p>0.05). The odds ratios (95% confidence interval) of MCP-1 G/G and CCR2 A/A genotypes for allergic rhinitis were not statistically significant, whereas, alleles frequencies of MCP-1 -2518G and CCR2 A of controls were various according to the ethnic background. CONCLUSION: Our result suggests MCP-1 -2518 A/G and CCR2 V64I polymorphisms are not part of the factors contributing to genetical susceptibility in the development of allergic rhinitis in Koreans.