Up-regulation of IGF Binding Protein-3 Inhibits Colonic Inflammatory Response.

BACKGROUND: The aggravating factors still remained unclear in inflammatory bowel disease (IBD). Despite many different therapeutic approaches, many patients do not respond to the therapy. The anti-inflammatory effect of insulin-like growth factor-binding protein-3 (IGFBP-3) was suggested because of its capability of nuclear factor-κB (NF-κB) signaling inhibition. Therefore, we hypothesized that the up-regulation of IGFBP-3 would inhibit an inflammatory process. METHODS: Lipopolysaccharides (LPS) treated intestinal epithelial cell 6 (IEC-6) and dextran sodium sulfate (DSS) induced colitis mice were used as colitis models. Exogenous IGFBP-3 expression was accomplished using the adenoviral vector system expressing IGFBP-3 (Ad/IGFBP-3). The inflammatory responses and relevant cellular responses in IEC-6 cells influenced by IGFBP-3 expression were evaluated by western blotting, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and reactive oxygen species (ROS) measurement. The severity of colitis was evaluated with the colon tissues of DSS-induced mouse model. RESULTS: We found that the IGFBP-3 expression reduced the production of inflammatory cytokines (cyclooxygenase-2, interleukin-1ß, tumor necrosis factor-α) and ROS formation. IGFBP-3 expression also induced cell viability and inhibited NF-κB activation. In line with this data, the severity of DSS-induced mouse colitis was greatly ameliorated by the treatment of IGFBP-3 expressing adenoviral particles characterized with less weight loss and preserved colon length compared with the mice treated with DSS alone. The histopathology of the colon showed the reducing signs of colitis in Ad/IGFBP-3 treated DSS-mice group. CONCLUSION: Therefore, our data suggest that Ad/IGFBP-3 up-regulation reduces colonic inflammatory response as a novel therapeutic protocol for IBD.

Erratum: Addition of Co-Authors: Up-regulation of IGF Binding Protein-3 Inhibits Colonic Inflammatory Response.

[This corrects the article e110 in vol. 33, PMID: 29573252.].

Awareness about past diagnosis and treatment history: nationwide survey of childhood cancer survivors and their parents.

OBJECTIVE: To assess the awareness of past medical history and long-term care issues of childhood cancer survivors (CCS) in Korea. METHODS: A nationwide survey was conducted on CCS and their parents in 10 regional cancer centers in Korea. Answers regarding cancer diagnosis and treatment history were compared with the treatment summary and categorized into three ('specific,' 'general,' and 'no') or two ('yes' and 'no') groups. RESULTS: Out of 343 contacts, 293 dyads completed the survey, and 281 dyads were analyzed. Awareness of cancer diagnosis was mostly specific for parents (76.5%) and CCS (35.2%). Awareness of anti-cancer treatment exposure was mostly general (84.6% for surgery, 67.9% for chemotherapy, and 53.9% for hematopoietic stem cell transplantation) rather than specific. In particular, more than half of the parents were not aware of the exposure to cardiotoxic agents (72.9%) or radiation therapy (56.3%). Providing information about long-term side effects and prevention of secondary cancer was significantly correlated only with more concern and more follow-up visits (P ≤ 0.001, respectively), without correlation with more specific awareness of exposure to cardiotoxic agents or radiation. CONCLUSION(S): Most of the parents of CCS were not aware of treatment-related risk factors necessary for long-term care. Providing information was significantly correlated with more concern and more follow-up visits, without improving corresponding knowledge about their past medical history. Effort aimed towards improving awareness about risk factors, the manner of providing information, and the patient referral system within which we use this information is warranted.

A Case of Cap Polyposis with Epidermal Nevus in an Infant.

Cap polyposis is extremely rare in children. We report a case of an 11-month-old male infant who visited our hospital because of rectal prolapse and small amount of hematochezia lasting several days. He also had an epidermal nevus in the sacral area. Colonoscopy showed erythematous, multilobulated, circumferential, polypoid lesions with mucoid discharge from the rectum. He was diagnosed with cap polyposis by endoscopy and histologic examination. He was treated with surgical resection, and was closely followed up. In the relevant literature, there is no report of cap polyposis in an infant. We report the first case of cap polyposis in the youngest infant.

Delayed Diagnosis of Falciparum Malaria with Acute Kidney Injury.

Prompt malaria diagnosis is crucial so antimalarial drugs and supportive care can then be rapidly initiated. A 15-year-old boy who had traveled to Africa (South Africa, Kenya, and Nigeria between January 3 and 25, 2011) presented with fever persisting over 5 days, headache, diarrhea, and dysuria, approximately 17 days after his return from the journey. Urinalysis showed pyuria and hematuria. Blood examination showed hemolytic anemia, thrombocytopenia, disseminated intravascular coagulation, and hyperbilirubinemia. Plasmapheresis and hemodialysis were performed for 19 hospital days. Falciparum malaria was then confirmed by peripheral blood smear, and antimalarial medications were initiated. The patient's condition and laboratory results were quickly normalized. We report a case of severe acute renal failure associated with delayed diagnosis of falciparum malaria, and primary use of supportive treatment rather than antimalarial medicine. The present case suggests that early diagnosis and treatment is important because untreated tropical malaria can be associated with severe acute renal failure and fatality. Physicians must be alert for correct diagnosis and proper management of imported tropical malaria when patients have travel history of endemic areas.

Protein kinase CK2/PTEN pathway plays a key role in platelet-activating factor-mediated murine anaphylactic shock.

Platelet-activating factor (PAF) is a major mediator in the induction of fatal hypovolemic shock in murine anaphylaxis. This PAF-mediated effect has been reported to be associated with PI3K/Akt-dependent eNOS-derived NO. The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is phosphatidylinositol phosphate phosphatase, which negatively controls PI3K by dephosphorylating the signaling lipid, phosphatidylinositol 3,4,5-triphosphate. In this study, we examined the possible involvement of PTEN in PAF-mediated anaphylactic shock. Induction of anaphylaxis or PAF injection resulted in a rapid decrease in PTEN activity, followed by increases in PI3K activity and phosphorylation of Akt and eNOS. Systemic administration of adenoviruses carrying PTEN cDNA (adenoviral PTEN), but not the control AdLacZ, not only attenuated anaphylactic symptoms, but also reversed anaphylaxis- or PAF-induced changes in PTEN and PI3K activities, as well as phosphorylation of Akt and eNOS. We found that the decreased PTEN activity was associated with PTEN phosphorylation, the latter effect being prevented by the protein kinase CK2 inhibitor, DMAT. DMAT also inhibited anaphylactic symptoms as well as the anaphylaxis- or PAF-mediated PTEN/PI3K/Akt/eNOS signaling cascade. CK2 activity was increased by PAF. The present data provide, as the key mechanism underlying anaphylactic shock, PAF triggers the upstream pathway CK2/PTEN, which ultimately leads to the activation of PI3K/Akt/eNOS. Therefore, CK2/PTEN may be a potent target in the control of anaphylaxis and other many PAF-mediated pathologic conditions.

Hispidin analogue davallialactone attenuates carbon tetrachloride-induced hepatotoxicity in mice.

In this study the protective effects of davallialactone (1), isolated from Inonotus xeranticus, have been examined against carbon tetrachloride (CCl4-induced acute liver injury. Mice received subcutaneous injection of 1 (2.5, 5, and 10 mg/kg) for three days before CCl4 injection (1 mg/kg). Protection from liver injury by 1 was confirmed by the observation of decreased serum transaminases and diminished necrosis of liver tissue. Reduced hepatic injury was very similar to that observed with silymarin, a known hepatoprotective drug used in this work for comparison. The groups treated with 1 had reduced reactive oxygen species (ROS), reduced serum malonyldialdehyde levels, and increased levels of liver Cu/Zn superoxide dismutase, as compared to the CCl4 control group. The expression of heme oxygenase-1 in the liver tissue was increased and the activity of liver cytochrome P4502E1 was restored in the mice treated with 1. In addition, levels of serum tumor necrosis factor-alpha (TNF-α), inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2), numbers of macrophage, and cleaved caspase-3-positive hepatocytes were reduced in the groups treated with 1. These findings suggest that davallialactone has protective effects against CCl4-induced acute liver injury, and this protection is likely due to the suppression of ROS-induced lipid peroxidation and inflammatory response.

Adriamycin inhibits adipogenesis through the modulation of PPARγ and restoration of adriamycin-mediated inhibition of adipogenesis by PPARγ over-expression.

Adriamycin is an anti-cancer drug, effective against a wide range of cancers. However, its clinical application is limited by its cardiotoxicity. A number of reports suggest that adriamycin induces bodyweight loss also. The aim of this study was to investigate the effect of adriamycin on adipogenesis as bodyweight chancges can be directly correlated with adipocytes. Fat accumulation in 3T3-L1 pre-adipocytes, as a result of adipogenesis was detected using oil red O staining. We performed western immunoblot for the expression of adipocyte differentiation related genes to analyze the molecular mechanism of adriamycin-mediated inhibition of adipogenesis. Over-expression of target gene was done by using recombinant adenoviruses. Adriamycin inhibited adipogenesis in a dose-dependent manner. It was observed that adriamycin down-regulated the expression of PPARγ. Moreover, up-stream elements of PPARγ were also found to be down-regulated by adriamycin. Adriamycin might prevent bodyweight gain through inbibition of adipogenesis by the down-regulation of PPARγ and its up-stream transcriptional regulators like C/EBPß and KLF4. To reverse the adriamycin-mediated inhibition of adipogenesis, PPARγ was over-expressed by adenoviral mediated gene delivery. Over-expression of PPARγ partially restored adipogenesis. Moreover, the early regulators of adipogenesis were also found to be restored after the over-expression of PPARγ. Adriamycin down-regulates the expression of PPARγ which leads to prevention of bodyweight gain through inhibition of adipogenesis. Activation of PPARγ by either adenoviral mediated gene delivery or by using PPARγ agonist may be useful in controlling the bodyweight loss.

c-myb mediates inflammatory reaction against oxidative stress in human breast cancer cell line, MCF-7.

Emerging evidence suggests that oncogenes play an important role in the inflammatory reactions in cancer cells, but the precise molecular and cellular mechanisms linking the oncogenes to inflammation is unclear. This study examined the contribution of proto-oncogene c-myb to inflammation in MCF-7 breast cancer cells. An inflammatory response was elicited directly by the cells using an in vitro culture system whereby the cells were exposed to H(2) O(2) . Upon exposure to H(2) O(2) , the cells showed a local inflammatory response, as evidenced by matrix metalloproteinases (MMPs) and ICAM-1 expression. Significant up-regulation of the proto-oncogene c-myb also was observed under inflammatory conditions. c-myb, overexpressed in the cells by transducing with Ad/c-myb, showed an increase in MMPs and ICAM-1 expression under H(2) O(2) stimulation. Despite H(2) O(2) stimulation, the c-myb down-regulated cells by c-myb siRNA inhibit the expression of MMPs and ICAM-1. Among the MAPKs, ERK1/2 and SAPK/JNK were activated by the H(2) O(2) treatment. Interestingly, the H(2) O(2) -induced activation of ERK1/2 and SAPK/JNK was inhibited by siRNA c-myb. These results suggest that breast cancer cells may play a significant role in sustaining and amplifying the inflammation process through the activation of c-myb, which results in the activation of the ERK1/2 and SAPK/JNK pathway. This condition highlights the potential link between inflammation and its involvement in promoting breast cancer proliferation.

Fulminant type 1 diabetes mellitus in Korean adolescents.

Fulminant type 1 diabetes has recently been identified as a new subtype of idiopathic diabetes that is mostly found in Japanese adults. The aim of this study was to investigate the frequency as well as the clinical and laboratory characteristics of fulminant type 1 diabetes among Korean children with childhood-onset type 1 diabetes. One-hundred and fifty patients that had been newly diagnosed with type 1 diabetes over the past 10 years were included. These patients came from three hospitals. Out of the 150 patients, two female patients fulfilled the criteria for fulminant type 1 diabetes. They were negative for islet autoantibodies. The patients with fulminant type 1 diabetes had an older age of onset and a lower HbA1c than the patients with autoimmune or idiopathic type 1 diabetes. In addition, the patients with fulminant type 1 diabetes had increased serum aspartate aminotransferase, alanine aminotransferase and amylase levels, and decreased fasting serum C-peptide levels. The frequency of fulminant type 1 diabetes was 1.33% among all patients newly diagnosed with type 1 diabetes under the age of 16. Although this type of diabetes is more commonly an adult-onset disease, it is possible that fulminant type 1 diabetes has not yet been fully recognized in children and adolescence, and may be more common than initially thought.

c-myb stimulates cell growth by regulation of insulin-like growth factor (IGF) and IGF-binding protein-3 in K562 leukemia cells.

c-myb plays an important role in the regulation of cell growth and differentiation, and is highly expressed in immature hematopoietic cells. The human chronic myelogenous leukemia cell K562, highly expresses IGF-I, IGF-II, IGF-IR, and IGF-induced cellular proliferation is mediated by IGF-IR. To characterize the impact of c-myb on the IGF-IGFBP-3 axis in leukemia cells, we overexpressed c-myb using an adenovirus gene transfer system in K562 cells. The overexpression of c-myb induced cell proliferation, compared to control, and c-myb induced cell growth was inhibited by anti-IGF-IR antibodies. c-myb overexpression resulted in a significant increase in the expression of IGF-I, IGF-II, and IGF-IR, and a decrease in IGFBP-3 expression. By contrast, disruption of c-myb function by DN-myb overexpression resulted in significant reduction of IGF-I, IGF-II, IGF-IR, and elevation of IGFBP-3 expression. In addition, exogenous IGFBP-3 inhibited the proliferation of K562 cells, and c-myb induced cell growth was blocked by IGFBP-3 overexpression in a dose-dependent manner. The growth-promoting effects of c-myb were mediated through two major intracellular signaling pathways, Akt and Erk. Activation of Akt and Erk by c-myb was completely blocked by IGF-IR and IGFBP-3 antibodies. These findings suggest that c-myb stimulates cell growth, in part, by regulating expression of the components of IGF-IGFBP axis in K562 cells. In addition, disruption of c-myb function by DN-myb may provide a useful strategy for treatment of leukemia.

Immunogenicity and safety of a combined DTPa-IPV/Hib vaccine administered as a three-dose primary vaccination course in healthy Korean infants: phase III, randomized study.

We assessed the immunogenicity and safety of a three-dose primary vaccination schedule with the combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus/Haemophilus influenzae type b vaccine (DTPa-IPV/Hib) in Korean infants. In this phase III open-label, multicenter study (NCT01309646), healthy infants aged 42-69 days (randomized 1:1) received three doses of either pentavalent DTPa-IPV/Hib (DTPa-IPV/Hib group) or DTPa-IPV and Hib vaccines administered separately (DTPa-IPV+Hib group) at 2, 4, 6 months of age. The primary objective was to demonstrate non-inferiority of DTPa-IPV/Hib compared to DTPa-IPV+Hib vaccines in terms of immune responses to all vaccine antigens, 1 month post-dose 3. Solicited symptoms (local and general) were recorded during 4 days, and unsolicited adverse events (AEs) during 31 days, after each vaccination. Serious AEs (SAEs) were recorded throughout the study duration. The immunogenicity of the pentavalent DTPa-IPV/Hib vaccine was non-inferior compared to concomitant administration of DTPa-IPV+Hib vaccines. One month post-dose 3, nearly all infants had antibody levels above the seroprotective thresholds for anti-diphtheria toxoid, anti-tetanus toxoid, anti-polyribosyl-ribitol phosphate, and anti-poliovirus type 1, 2 and 3, and had antibody levels above the seropositive thresholds for anti-pertussis toxoid (PT), anti-filamentous hemagglutinin (FHA) and anti-pertactin (PRN) antibodies. A vaccine response for PT, FHA and PRN was observed in at least 96.7% of study participants. Anti-PRP geometric mean concentrations appeared lower for the DTPa-IPV/Hib group (8.456 µg/mL) than for the DTPa-IPV+Hib group (18.700 µg/mL). In both groups, the most common solicited symptoms were injection site redness and irritability. Fifty-seven SAEs were reported throughout the study; none were considered to be vaccination related.

Laboratory formulated magnetic nanoparticles for enhancement of viral gene expression in suspension cell line.

One factor critical to successful gene therapy is the development of efficient delivery systems. Although advances in gene transfer technology including viral and non-viral vectors have been made, an ideal vector system has not yet been constructed. Due to the growing concerns over the toxicity and immunogenicity of viral DNA delivery systems, DNA delivery via improve viral routes has become more desirable and advantageous. The ideal improve viral DNA delivery system should be a synthetic materials plus viral vectors. The materials should also be biocompatible, efficient, and modular so that it is tunable to various applications in both research and clinical settings. The successful steps towards this improve viral DNA delivery system is demonstrated: a magnetofection system mediated by modified cationic chitosan-coated iron oxide nanoparticles. Dense colloidal cationic iron oxide nanoparticles serve as an uptake-enhancing component by physical concentration at the cell surface in presence of external magnetic fields; enhanced viral gene expression (3-100-fold) due to the particles is seen as compared to virus vector alone with little virus dose.

Adenovirus-mediated expression of dominant negative c-myb induces apoptosis in head and neck cancer cells and inhibits tumor growth in animal model.

The recent demonstration of aberrant expression of the c-myb proto-oncogene in various cancers suggests that c-myb plays an important role in the development of cancer. On this basis, it has been proposed that ablation of c-myb function might be an effective approach for therapy of c-myb dependent malignancies. We previously used a dominant negative c-myb (DN-myb) construct to induce apoptosis in K562 cells. In this study, DN-myb was expressed in an adenovirus-mediated gene delivery system and introduced into head and neck squamous cell carcinoma cells (HNSCC) in vitro and in vivo to examine its tumor suppressive function and its potential in HNSCC gene therapy. Over expression of DN-myb in HNSCC cells inhibited in vitro cell proliferation, expression of growth factors such as IGF-I, -II, IGF-1R, and VEGF, inhibited Akt/PKB pathway activation, and enhanced induction of apoptosis. Similarly, in vivo administration of DN-myb retarded tumor-growth. Our results support a role for DN-myb in inducing apoptosis and tumor suppression, and, furthermore, suggest that DN-myb gene therapy might provide a powerful tool for treatment of c-myb dependent malignancies such as HNSCC.

Carcinosarcoma of the rectosigmoid colon in a 13-year-old girl.

Reported herein is an unusual case of carcinosarcoma of the colon. A 13-year-old girl was transferred to Chonbuk National University Hospital, Korea with a known pelvic mass. CT and magnetic resonance imaging confirmed a large pelvic mass. A sarcoma was diagnosed following colonoscopic biopsy. An ultra-low anterior resection with pelvic lymph node dissection was performed. The tumor consisted of a well-differentiated adenocarcinoma showing strong immunoreactivity to epithelial markers (pancytokeratin, cytokeratin 7, cytokeratin 19, cytokeratin 20, epithelial membrane antigen, and CEA) and a sarcomatous lesion with strong diffuse vimentin expression but no immunoreactivity to any of the six epithelial markers. Carcinosarcomas of the colon are extremely rare, and all reported cases involve adults. To the authors' knowledge, this is the first reported case of a carcinosarcoma of the colon in a child.

Pax9 mediated cell survival in oral squamous carcinoma cell enhanced by c-myb.

Paired box gene 9 (Pax9) and c-myb are transcription factors that regulate the expression of the genes involved in mediating cell proliferation, resistance to apoptosis, and migration. However, the function of Pax9 in oral squamous cell carcinoma (OSCC) is virtually unknown. This study examined the anti-apoptotic roles of Pax9 and c-myb, and clarified interaction between the two genes in KB cells. Inhibition of Pax9 caused the induction of apoptosis with enhanced cleavage of caspase-3 and PARP, accelerated Bax, and reduced Bcl-2 expression. Transducing c-myb cells with adenovirus c-myb (Ad/c-myb) were induced cell growth and inhibited apoptosis, but dominant-negative myb cells (Ad/DN-myb) were not affected. Pax9 was upregulated in the Ad/c-myb cells with simultaneous decrease in the Ad/DN-myb infection. However, c-myb remained unaffected in the Pax9 small interfering RNA (siRNA) transfected cells. Moreover, the Pax9 siRNA transfected cells and Ad/DN-myb infected cells were able to arrest the cell cycle at the G(0) phase. This suggests that Pax9 and c-myb expression in KB cells is essential for cell growth, and survival is enhanced by c-myb. Disrupting the function of c-myb and Pax9 could be a potential target for cancer treatment.

N-hexanoyl chitosan-stabilized magnetic nanoparticles: enhancement of adenoviral-mediated gene expression both in vitro and in vivo.

We developed hexanoyl chloride-modified chitosan (Nac-6) stabilized iron oxide nanoparticles (Nac-6-IOPs) as magnetic nanoparticles for viral gene (Ad/LacZ) delivery via magnetofection. This vector, Nac-6-IOPs/Ad/LacZ, binds to K562 cells in the presence of external magnetic fields and results in enhanced expression of the transgene in those cells that do not exhibit the coxsackie-adenovirus receptor (CAR). Our results demonstrate that Nac-6-IOPs/Ad/LacZ is able to transduce K562 cells specifically with reduced infection of CAR- cells. The dramatic enhancement in intracellular trafficking of the adenovirus without genetically modified vesicles can lead to enhanced nuclear transfer, especially in CAR- cells. In vivo magnetofection results also clearly demonstrated that the present Nac-6-IOPs could be applied in other cell lines. Whether cells or organs, in the presence of magnetic fields Nac-6-IOPs/Ad/LacZ has high transduction efficiency. The newly formulated Nac-6-IOPs, introduced by magnetofection, provide a high-throughput gene screening both in vitro and in vivo.

Rebound thymic hyperplasia after adrenalectomy in a patient with Cushing syndrome caused by adrenocortical adenoma: A case report.

RATIONALE: The development of rebound thymic hyperplasia (RTH) has been reported in patients who have recovered from stressful conditions such as surgery and steroid therapy. We report a case of RTH following the resolution of hypercortisolism after adrenalectomy for the treatment of adrenocortical adenoma in a patient with Cushing syndrome. PATIENT CONCERNS: A 5-month-old female infant with a history of overeating, hirsutism, and excessive weight gain for the previous 2 months was referred to the hospital. The laboratory results revealed elevated 24-hour urinary free cortisol levels. An overnight dexamethasone suppression test showed no response. Abdominal imaging revealed a right-sided suprarenal mass measuring 4_3cm. Histology showed an adrenocortical adenoma. Thus, she underwent a right adrenalectomy. DIAGNOSES: The patient showed clinical improvement with weight loss and normal cortisol levels over the next 4 months. Six months after the operation, a chest computed tomography showed enlargement of the left thymic lobe, which was previously nonexistent. INTERVENTIONS: A fine needle aspiration biopsy was performed, and histological examination revealed diffuse thymic hyperplasia. OUTCOMES: At the 1-year follow-up, the chest imaging studies showed resolution of the RTH. LESSIONS: An understanding of RTH after adrenalectomy as a treatment for cortisol-producing adrenocortical tumors is important for the prevention of unnecessary surgical intervention and therapy.

A Case of a Girl with Arnold-Chiari Type 1 Malformation with Precocious Puberty.

A small percentage of individuals have the neurological anomaly of central precocious puberty (CPP). Common neurologic causes of CPP include a tumor or congenital lesions. Although Arnold-Chiari malformation can be caused by congenital or acquired causes, it is unusual in patients with CPP. We present the case of a girl aged 4.5 years who complained of breast budding. Her neurological examination and growth pattern were normal. She had no endocrinological abnormality, except for true precocious puberty. We performed brain magnetic resonance imaging, which showed an Arnold-Chiari type 1 malformation. Currently, this case represents the youngest girl who exhibited both Arnold-Chiari type 1 malformation and precocious puberty. Furthermore, it is likely that there is a meaningful association between the brain lesion and precocious puberty in this case.

Preproghrelin Leu72Met polymorphism predicts a lower rate of developing renal dysfunction in type 2 diabetic nephropathy.

OBJECTIVE: Ghrelin is a novel peptide hormone, which exerts somatotropic, orexigenic and adipogenic effects. Recent studies have shown that the preproghrelin Leu72Met polymorphism is associated with serum creatinine (Scr) concentration in type 2 diabetes; 72Met carriers exhibited lower Scr levels as compared with the 72Met non-carriers. We hypothesized that the preproghrelin Leu72Met polymorphism is associated with a lower rate of developing renal dysfunction in patients with type 2 diabetic nephropathy. DESIGN: The preproghrelin Leu72Met polymorphism was investigated using PCR techniques in 138 patients with diabetic nephropathy divided into two groups, one with normal renal function and the other with renal dysfunction. METHODS: Determination of the frequency of the preproghrelin Leu72Met polymorphism was the main outcome measure. RESULTS: The frequency of the Leu72Met polymorphism in diabetic nephropathy was significantly lower in patients with renal dysfunction (15.9%, P < 0.01) than in patients with normal renal function (42.0%) or in the diabetes control group (40.6%). The Leu72Met polymorphism was also associated with serum total cholesterol levels in diabetic nephropathy patients with renal dysfunction; the 72Met carriers had lower total cholesterol levels than the 72Met non-carriers (P < 0.05). CONCLUSION: These data suggest that 72Met carrier status may be used as a marker predicting a lower chance of developing renal dysfunction in diabetic nephropathy.