No abstract

HRPT2, the gene associated with hyperparathyroidism-jaw tumor (HPT-JT) syndrome, was previously mapped to 1q24-q32. It was recently cloned, and several germline mutations were found to predispose to HPT-JT syndrome. We sequenced the complete HRPT2 coding sequence and splice-junctional regions in a Korean family with HPT-JT syndrome and identified a novel germline mutation, IVS2-1G>A in intron 2, that caused the autosomal dominant trait of HPT-JT syndrome in this family. RT-PCR and sequencing of the transcripts revealed that this splicing mutation generated alternative splicing errors leading to the formation of two different transcripts, one with exon 3 deleted, the other lacking the first 23 bp of exon 3 due to the use of an internal splice acceptor in exon 3. Translation of both transcripts results in premature termination. In addition, we detected two novel somatic mutations of HRPT2 in malignant parathyroid tumors from the affected individuals. One, 85delG, causes premature termination; the other, an 18 bp in-frame deletion of 13_30delCTTAGCGTCCTGCGACAG, suggests that this region may be important in the development of the parathyroid carcinomas in HPT-JT syndrome. These findings provide further evidence that mutation of HRPT2 is associated with the formation of parathyroid tumors in HPT-JT syndrome.

The aim of the present study was to evaluate the effects on the susceptibility to colorectal cancer (CRC) of genetic polymorphisms in P-glycoprotein (PGP) and the metabolic enzymes cytochrome P450 1A2 (CYP1A2) and flavin-containing monooxygenase 3 (FMO3). We analyzed five single-nucleotide polymorphisms (SNP) in 93 cancer-free volunteers and 111 patients with CRC: one common genetic variant of the PGP-encoding MDR1 gene and four SNP in genes for metabolic enzymes (two SNP in FMO3 and two SNP in CYP1A2). The genotypes and allele frequencies of the MDR1/C3435T, FMO3/G488A, FMO3/A923G and CYP1A2/G-3860 A polymorphisms were not significantly different in cancerfree subjects and CRC patients. However, a significant association was found between the CYP1A2/A-163C polymorphism and the risk of CRC, particularly in elderly (>55 years) subjects and smokers. A phenotyping study in normal smokers showed that the CYP1A2 activity of subjects with the CYP1A2/− − − −163 AA genotype was significantly lower than that of subjects carrying the CYP1A2 (1-6) The carcinogens that cause the development of CRC enter the body as (pro)carcinogens via transporters, (7)(8)(9) and are activated to carcinogens or eliminated by various enzymes.(10) These toxicokinetic-related proteins are also controlled by our genetic background (e.g. by genetic polymorphisms). In considering the effects of genetic polymorphisms on the toxicokinetic profiles of xenobiotics, particularly (pro) carcinogens, we must evaluate the combined effects of genetic polymorphisms in both transporters and metabolic enzymes.To date, numerous studies have been conducted to correlate the genetic polymorphisms of single proteins and the risk of disease development or progression. In particular, genetic polymorphisms in drug metabolizing enzymes, such as the cytochrome P450 1 (CYP1A) family, (11,12) glutathione Stransferases, (13) N-acetyltransferases (14) and UDP-glucuronosyltransferases, (15) are the most well-known and important genetic factors in the development of CRC. Flavin-containing monooxygenase 3 (FMO3) is one of the major hepatic metabolic enzymes that catalyze the NADPH-dependent attachment of molecular oxygen to endogenous and foreign chemicals containing nucleophilic N, S and P heteroatoms. There are few studies of the relationship between FMO3 activity and carcinogenesis. A drug transporter, P-glycoprotein (PGP), is a recognized gatekeeper that limits the accumulation of xenobiotics in the body by facilitating ATPconsuming efflux. Recently, studies of the relationship between MDR1 polymorphisms and disease susceptibility have been conducted. (16,17) However, there has been no report of the relationship between the combined genetic polymorphisms of drug transporters and metabolic enzymes and CRC development.Against this background, we analyzed the common genetic polymorphisms in the genes for the drug transporter MDR1 and the metabolic enzymes CYP1A2 and FMO3, and attempted to elucidate the association between these polymorphisms and sporadic CRC in Koreans. We a...

AIM:To analyze the risk factors of pancreatic leakage after pancreaticoduodenectomy. METHODS:We r e t r o s p e c t i v e l y r e v i e w e d 1 7 2 consecutive patients who had undergone pancreaticoduodenectomy at Inha University Hospital between April 1996 and March 2006. We analyzed the pancreatic fistula rate according to the clinical characteristics, the pathologic and laboratory findings, and the anastomotic methods. RESULTS: The incidence of developing pancreatic fistulas in patients older than 60 years of age was 21.7% (25/115), while the incidence was 8.8% (5/57) for younger patients; the difference was significant (P = 0.03). Patients with a dilated pancreatic duct had a lower rate of post-operative pancreatic fistulas than patients with a non-dilated duct (P = 0.001). Other factors, including clinical features, anastomotic methods, and pathologic diagnosis, did not show any statistical difference. CONCLUSION: O u r s t u d y d e m o n s t ra t e d t h a t pancreatic fistulas are related to age and a dilated pancreatic duct. The surgeon must take these risk factors into consideration when performing a pancreaticoduodenectomy.

OBJECTIVE -We investigated the link between lipid-rich skeletal muscle, namely lowdensity muscle, and insulin resistance in Korea.RESEARCH DESIGN AND METHODS -Abdominal adipose tissue areas and midthigh skeletal muscle areas of 75 obese nondiabetic subjects (23 men, 52 women; mean age Ϯ SD, 41.9 Ϯ 14.1 years) were measured by computed tomography (CT). The midthigh skeletal muscle areas were subdivided into low-density muscle (0 to ϩ30 Hounsfield units) and normal-density muscle (ϩ31 to ϩ100 Hounsfield units). The homeostasis model assessment (HOMA) score was calculated to assess whole-body insulin sensitivity.RESULTS -The abdominal visceral fat area and the midthigh low-density muscle area were found to be well correlated with the HOMA score (r ϭ 0.471, P Ͻ 0.01 and r ϭ 0.513, P Ͻ 0.01, respectively). The correlation between low-density muscle area and insulin resistance persisted after adjusting for BMI or total body fat mass (r ϭ 0.451, P Ͻ 0.01 and r ϭ 0.522, P Ͻ 0.01, respectively) and even after adjusting for abdominal visceral fat area (r ϭ 0.399, P Ͻ 0.01).CONCLUSIONS -The midthigh low-density muscle area seems to be a reliable determinant of insulin resistance in Korean obese nondiabetic patients. Diabetes Care 26:1825-1830, 2003T he close relationship between abdominal adiposity and insulin resistance has been described in previous studies (1-3). Moreover, visceral adipose tissue is well recognized to be significantly related to insulin resistance of obese type 2 diabetic patients and even patients with normal weight (4,5).Recently, the role of intramuscular lipid components in insulin resistance became the subject of attention (6 -8). Lowdensity muscle represents lipid-rich skeletal muscle, which includes fat components between and inside the muscle fibers. Many other studies have already shown that low-density muscle is significantly related to insulin resistance in obese type 2 diabetic patients. However, this relation has not been investigated in Korea, where the prevalence of both obesity and diabetes is relatively low. Therefore, the current study was undertaken to investigate the potential link between low-density muscle and insulin resistance in the Korean population. RESEARCH DESIGN AND METHODS SubjectsA total of 75 subjects (23 men, 52 women; mean age Ϯ SD, 41.9 Ϯ 14.1 years) with sedentary lifestyle were enrolled in this cross-sectional study. Of these, 69 patients were obese (BMI Ͼ25 kg/m 2 ) and the remainder were overweight (BMI 23-25 kg/m 2 ), according to the revised definition of adult obesity in the AsianPacific race proposed at the Hong Kong meeting (9). A total of 33 premenopausal women and 19 women with natural menopause (mean age Ϯ SD, 31.2 Ϯ 7.8 and 54.8 Ϯ 7.9 years, respectively) were included. Subjects were divided into a normal glucose tolerance group (n ϭ 46) and an impaired glucose tolerance group (n ϭ 29), according to the results of an oral glucose tolerance test (OGTT). Individuals with a history of or evidence of hypertension, any type of diabetes, or cardiovascular disea...