Biomedical subjects

Lei Chen

Publications and source records attributed to Lei Chen.

At least 127 records · Page 7Linked to original sources

PubMed2004

GABAergic neurotransmission in globus pallidus and its involvement in neurologic disorders.

The globus pallidus occupies a critical position in the 'indirect' pathway of the basal ganglia and, as such, plays an important role in the modulation of movement. In recent years, the importance of the globus pallidus in the normal and malfunctioned basal ganglia is emerging. However, the function and operation of various transmitter systems in this nucleus are largely unknown. GABA is the major neurotransmitter involved in the globus pallidus. By means of electrophysiological recording, immunohistochemistry and behavioral studies, new information on the distribution and functions of the GABAergic neurotransmission in the rat globus pallidus has been generated. Morphological studies revealed the existence of GABA(A) receptor, including its benzodiazepine binding site, and GABA(B) receptor in globus pallidus. At subcellular level, GABA(A) receptors are located at the postsynaptic sites of symmetric synapses (putative GABAergic synapses). However, GABA(B) receptors are located at both pre- and postsynaptic sites of symmetric, as well as asymmetric synapses (putative excitatory synapses). Consistent with the morphological results, functional studies showed that activation of GABA(B) receptors in globus pallidus reduces the release of GABA and glutamate by activating presynaptic auto- and heteroreceptors, and hyperpolarizes pallidal neurons by activating postsynaptic receptors. In addition to GABA(B) receptor, activation of GABA(A) receptor benzodiazepine binding site and blockade of GABA uptake change the activity of globus pallidus by prolonging the duration of GABA current. In agreement with the in vitro effect, activation of GABA(B) receptor, GABA(A) receptor benzodiazepine binding site and blockade of GABA uptake cause rotation in behaving animal. Furthermore, the GABA system in the globus pallidus is involved in the etiology of Parkinson's disease and regulation of seizures threshold. It has been demonstrated that the abnormal hypoactivity and synchronized rhythmic discharge of globus pallidus neurons associate with akinesia and resting tremor in parkinsonism. Recent electrophysiological and behavioral studies indicated that the new anti-epileptic drug, tiagabine, is functional in globus pallidus, which may present more information to understand the involvement of globus pallidus in epilepsy.

Animals↗

PubMed2004

Oxidative DNA damage and DNA repair enzyme expression are inversely related in murine models of fatty liver disease.

Mitochondrial generation of reactive oxygen species (ROS) is increased in mice with fatty livers induced by genetic obesity, chronic consumption of ethanol, or methionine/choline-deficient diets. Both nuclear and mitochondrial (mt) DNA are targets for ROS-induced damage and accumulate hydroxylated bases, such as 8-hydroxy-2'-deoxyguanosine (8-oxoG) and base substitution of adenine with 8-oxoG (A*8-oxoG), that introduce mutations that promote cancer as well as cell death. The mammalian homolog of the bacterial DNA mismatch repair enzyme MutY (MYH) removes A*8-oxoG from nuclear and mtDNA, reduces 8-oxoG accumulation, and restores genomic stability after ROS exposure. Cumulative damage to mtDNA occurs as fatty liver disease progresses. Therefore, differences in hepatic MYH activity may influence the severity of fatty liver disease. To evaluate this hypothesis, we compared mtH2O2 production, MYH expression, oxidative DNA damage, and hepatocyte death in healthy mice and different mouse models of fatty liver disease. The results show that diverse causes of steatohepatitis increase mtROS production, limit repair of mtDNA, and oxidatively damage DNA. However, there are important differences in the DNA repair response to oxidant stress among mouse models of fatty liver disease. Independent of the degree of mtROS generation, models with the least MYH exhibit the greatest accumulation of 8-oxoG and the most hepatocyte death. These findings raise the intriguing possibility that inherited or acquired differences in DNA repair enzyme activity may underlie some of the interindividual differences in fatty liver disease outcomes.

Animals↗

PubMed2004

Subcellular localization of GABAB receptor subunits in rat globus pallidus.

The inhibitory amino acid gamma-aminobutyric acid (GABA) is the major neurotransmitter in the globus pallidus. Although electrophysiological studies have indicated that functional GABA(B) receptors exist in rat globus pallidus, the subcellular localization of GABA(B) receptor subunits and their spatial relationship to glutamatergic and GABAergic synapses are unknown. Here, we use pre-embedding immunogold labeling to study the subcellular localization of GABA(B) receptor subunits, GABA(B1) and GABA(B2), in globus pallidus neurons and identified populations of afferent terminals. Immunolabeling for GABA(B1) and GABA(B2) was observed throughout the globus pallidus, with GABA(B1) more strongly expressed in perikarya and GABA(B2) mainly expressed in the neuropil. Electron microscopic analysis revealed that the majority of GABA(B1) labeling was localized within the cytoplasm, whereas most of GABA(B2) labeling was associated with the plasma membrane. At the subcellular level, both the GABA(B1) and GABA(B2) immunogold labeling was localized at pre- and postsynaptic sites. At asymmetric, putative excitatory, synapses, GABA(B1) and GABA(B2) immunogold labeling was found at perisynaptic sites of both pre- and postsynaptic specializations. Double immunolabeling, using the vesicular glutamate transporter 2 (VGLUT2), revealed the glutamatergic nature of most immunogold-labeled asymmetric synapses. At symmetric, putative GABAergic, synapses, including those formed by anterogradely labeled striatopallidal terminals, GABA(B1) and GABA(B2) immunogold labeling was found in the main body of both pre- and postsynaptic specializations. These results demonstrate the existence of presynaptic GABA(B) auto- and heteroreceptors and postsynaptic GABA(B) receptors, which may be involved in modulating synaptic transmission in the globus pallidus.

Animals↗

PubMed2004

A novel diagnostic marker, p28GANK distinguishes hepatocellular carcinoma from potential mimics.

PURPOSE: To investigate the sensitivity, specificity, and spatial distribution of the product of p28 gene (p28(GANK) protein) in human hepatocellular carcinoma (HCC) and nonhepatocellular carcinomas in relation to immunostaining with Cytokeratin 18 (CK18), alpha-fetoprotein (AFP), and Hepatocyte paraffin 1 (HepPar1). METHOD: In this retrospective study, formalin-fixed paraffin-embedded tissues from 24 HCCs, five intrahepatic cholangiocarcinomas (ICC), five combined hepatocellular cholangiocarcinomas (C-HCC-CC) and mine metastatic hepatic carcinomas (MHC) were immunostained for p28(GANK) as well as CK18, AFP and HepPar1. Only cases with more intensified staining in carcinoma contrast to the adjacent liver tissues were accepted as positive. RESULT: In HCC, p28(GANK) was expressed restrictively in hepatocytes of both para-lesion and carcinoma liver tissues, while absent in the bile duct epithelial cells, Kupffer cells, and other interstitial cells. The positive staining of p28(GANK) was noted in 16 (66.7%) specimens of HCC and three (60.0%) specimens of C-HCC-CC, and no specific lesion staining was found in all tested specimens of ICC and MHC. Sensitivity and specificity for hepatocyte-originated carcinoma were, respectively, 65.5% and 100% for p28(GANK), 79.3% and 85.2% for CK18, 20.7% and 100% for AFP, 79.3% and 92.0% for HepPar1. CONCLUSION: The hepatocytic staining for p28(GANK) is clearly useful in differentiating hepatocyte-originated carcinoma from non-HCC. p28(GANK) may be used as an ancillary marker for the diagnosis of HCC.

Biomarkers, Tumor↗

PubMed2004

Expression of gonadotropin-releasing hormone receptor and effect of gonadotropin-releasing hormone analogue on proliferation of cultured gastric smooth muscle cells of rats.

AIM: To investigate the expression of gonadotropin-releasing hormone (GnRH) receptor and the effects of GnRH analog (alarelin) on proliferation of cultured gastric smooth muscle cells (GSMC) of rats. METHODS: Immunohistochemical ABC methods and in situ hybridization methods were used to dectect protein and mRNA expression of GnRH receptor in GSMC, respectively. Techniques of cell culture, OD value of MTT test, measure of (3)H-TdR incorporation, average fluorescent values of proliferating cell nuclear antigen (PCNA) and flow cytometric DNA analysis were used in the experiment. RESULTS: The cultured GSMC of rats showed immunoreactivity for GnRH receptor; positive staining was located in cytoplasm. GnRH receptor mRNA hybridized signals were also detected in cytoplasm. When alarelin (10(-9), 10(-7), 10(-5) mol/L) was administered into the medium and incubated for 24 h, OD value of MTT, (3)H-TdR incorporation and average fluorescent values of PCNA all decreased significantly as compared with the control group (P<0.05). The maximum inhibitory effect on cell proliferation was achieved a concentration of 10(-5) mol/L and it acted in a dose-dependent manner. Flow cytometric DNA analysis revealed that alarelin could significantly enhance ratio of G(1) phase and decrease ratio of S phase of GSMC of rats (P<0.05). The maximum inhibitory effect on ratio of S phase was at the concentration of 10(-5) mol/L and also acted in a dose-dependent manner. CONCLUSION: Our data suggest that GnRH receptor can be expressed by GSMC of rats. GnRH analogue can directly inhibit proliferation and DNA synthesis of rat GSMC through GnRH receptors.

Animals↗

PubMed2004

Preparation and characterization of silver/TiO2 composite hollow spheres.

Silver-coated poly(methyl acrylic acid) (PSA) core-shell colloid particles were prepared by an in situ chemical reduction method. Crystalline silver/titania composite hollow spheres were obtained by coating the as-prepared PSA/silver particles with an amorphous titania layer and subsequently calcining in Ar atmosphere. SEM and TEM investigation indicated that the size of the as-prepared PSA/silver and PSA/silver/TiO(2) core-shell particles and silver/titania composite hollow particles was fairly uniform and the wall thickness of the hollow spheres was in the range of 40-80 nm. UV-vis absorption spectra were recorded to investigate their optical properties.

Colloids↗

PubMed2004

[A comparison of the application of two working definitions of metabolic syndrome in Chinese population].

OBJECTIVE: To compare the significance of the application of the working definition for metabolic syndrome (MS) proposed by the World Health Organization (WHO) in 1999 and the one proposed by the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III) in 2001. METHODS: Data of 2048 subjects, aged 20-74, 896 males and 1152 females, with complete laboratory data, including plasma glucose, lipid profile, blood pressure, serum insulin, urine albumin and creatinine, were gathered from the data of baseline survey on obesity and its co-morbidities conducted in Huayang and Caoyang communities, Shanghai, from 1999 to 2001. MS was diagnosed according to these two definitions respectively. RESULTS: (1) The age-adjusted MS prevalence rates were 17.14% and 10.95% according to the WHO (1999) and ATP III (2001) respectively, the former being significantly higher than the latter. (2) A total of 445 subjects were diagnosed as having MS. The agreement in the diagnosis of MS using two definitions was about 45.17%. 42.02% of the subjects had MS only under the WHO (1999) definition, while 12.81% of the subjects had MS under the ATP III (2001) definition. (3) The prevalence rate of hyperglycemia and central obesity as defined by WHO (1999) definition were 1.74 and 4.38 times higher than those defined by ATP III (2001) definition (16.74% vs 9.57%, 33.04% vs 7.54% respectively). (4) In comparison with non-MS subjects, the body mass index, waist-to-hip ratio, blood pressure, blood glucose, insulin resistant index (HOMA-IR), and albumin-to-creatinine ratio were all significantly increased in MS subjects. CONCLUSION: Both definitions for MS can reflect the clustering degree of risk factors of cerebrovascular and cardiovascular diseases. The WHO definition of MS can better reflect the characteristics of MS in Chinese than the definition proposed by ATP III, however it needs more measurements and costs more. A simple method with high detection ability remains to be worked out.

Albuminuria↗

PubMed2004

Interrelationship of growth differentiation factor 9 and inhibin in early folliculogenesis and ovarian tumorigenesis in mice.

To investigate the interrelationship of inhibin alpha and growth differentiation factor 9 (GDF9) during early folliculogenesis, we generated mice lacking both inhibin alpha and GDF9. Our findings on these Inha Gdf9 double-mutant mice are as follows: 1). females develop ovarian tumors and a cachexia-like wasting syndrome, resembling mice lacking inhibin alpha alone. This indicates that the granulosa cells are competent to proliferate despite the lack of GDF9; 2). follicular development progresses to multiple-layer follicle stages before tumorigenesis. This demonstrates that the up-regulation of inhibin alpha in the Gdf9 knockout ovary directly prevents the proliferation of the granulosa cells at the primary follicle stage, an effect that is released in the absence of inhibin alpha; 3). a morphological theca forms around the preantral follicles with no detectable selective theca markers [i.e. 17alpha-hydroxylase (Cyp17), LH receptor (Lhr), and Kit]. These results indicate that the theca recruitment can occur independently of GDF9, but the differentiation of thecal cells is blocked; and 4). inhibin/activin subunits betaA, betaB, and Kit ligand (Kitl) mRNA are highly up-regulated, suggesting that the increased activins and KITL play functional roles in early folliculogenesis. Thus, GDF9 appears to function indirectly to regulate early granulosa cell proliferation and theca recruitment in vivo.

Activins↗

PubMed2004

Negative regulation of hepatocellular carcinoma cell growth by signal regulatory protein alpha1.

Signal regulatory protein (SIRP) alpha1 is a member of the SIRP family that undergoes tyrosine phosphorylation and binds SHP-2 tyrosine phosphatase in response to various mitogens. The expression levels of SIRPalpha1 were decreased in HCC tissues, compared with the matched normal tissues. Exogenous expression of wild type SIRPalpha1, but not of a mutant SIRPalpha1 lacking the tyrosine phosphorylation sites, in SIRPalpha1-negative Huh7 human HCC cells resulted in suppression of tumor cell growth both in vitro and in vivo. Treatment of Huh7 transfectants with EGF or HGF induced tyrosine phosphorylation of SIRPalpha1 and its association with SHP-2, which were accompanied by reduced ERK1 activation. Expression of SIRPalpha1 significantly suppressed activation of NF-kappaB and also sensitized Huh7 cells to TNFalpha or cisplatin-induced cell death. In addition, SIRPalpha1-transfected Huh7 cells displayed reduced cell migration and cell spreading in a fashion that was dependent on SIRPalpha1/SHP-2 complex formation. In conclusion, a negative regulatory effect of SIRPalpha1 on hepatocarcinogenesis is exerted, at least in part, through inhibition of ERK and NF-kappaB pathways.

Antigens, Differentiation↗

PubMed2004

Cloning and characterization of an mRNA encoding a novel G protein alpha-subunit abundant in mantle and gill of pearl oyster Pinctada fucata.

Nacre formation is an ideal model to study biomineralization processes. Although much has been done about biomineralization mechanism of nacre, little is known as to how cellular signaling regulates this process. We are interested in whether G protein signaling plays a role in mineralization. Degenerate primers against conserved amino acid regions of G proteins were employed to amplify cDNA from the pearl oyster Pinctada fucata. As a result, the cDNA encoding a novel G(s)alpha (pfG(s)alpha) from the pearl oyster was isolated. The G(s)alpha cDNA encodes a polypeptide of 377 amino acid residues, which shares high similarity to the octopus (Octopus vulgaris) G(s)alpha. The well-conserved A, C, G (switch I), switch II functional domains and the carboxyl terminus that is a critical site for interaction with receptors are completely identical to those from other mollusks. However, pfG(s)alpha has a unique amino acid sequence, which encodes switch III and interaction sites of adenylyl cyclase respectively. In situ hybridization and Northern blotting analysis revealed that the oyster G(s)alpha mRNA is widely expressed in a variety of tissues, with highest levels in the outer fold of mantle and epithelia of gill, the regions essential for biomineralization. We also show that overexpression of the pfG(s)alpha in mammalian MC3T3-E1 cells resulted in increased cAMP levels. Mutant pfG(s)alpha that has impaired CTX substrate diminished its ability to induce cAMP production. Furthermore, the alkaline phosphatase (ALP) activity, an indicator for mineralization, is induced by the G(s)alpha in MC3T3-E1 cells. These results indicated that G(s)alpha may be involved in regulation of physiological function, particularly in biological biomineralization.

Alkaline Phosphatase↗

PubMed2004

Electrophysiological and behavioral effects of zolpidem in rat globus pallidus.

The globus pallidus is believed to play a critical role in the normal function of the basal ganglia, and abnormal activity of its neurons may underlie some basal ganglia motor symptoms. A high density of benzodiazepine binding sites on GABAA receptors has been reported in the rat globus pallidus. The present study investigates the effect of activating the benzodiazepine site by the agonist zolpidem. In in vitro slices, 100 nM of zolpidem significantly prolonged the half decay time of both miniature and spontaneous inhibitory postsynaptic currents by 30.1 +/- 3.0% (n=12) and 17.8 +/- 2.4% (n=16), respectively, with no effect on their amplitudes and frequencies. In the behaving animal, when zolpidem was microinjected into the globus pallidus unilaterally, it caused a robust ipsilateral rotation (26.4 +/- 2.4 turns/30 min, n=8), significantly higher than that of control animals receiving vehicle injection (1.3 +/- 1.6 turns/30 min, n=6). This effect was in agreement with the in vitro effect of zolpidem in enhancing the action of GABA on postsynaptic GABAA receptors. All the effects of zolpidem, in vitro or in vivo, were sensitive to the benzodiazepine antagonist flumazenil, confirming the specificity on the benzodiazepine site. This finding on the effect of zolpidem on motor behavior provides a rationale for further investigations into its potential in the treatment of motor disorders originating from the basal ganglia.

Action Potentials↗

PubMed2004

Disassociated increases of adrenomedullin in the rat cerebrospinal fluid and plasma after salt loading and systemic administration of lipopolysaccharide.

To determine the role of adrenomedullin (AM) in the fluid electrolyte homeostasis and endotoxin shock, cerebral spinal fluid (CSF) and plasma were sampled from rats after respective challenges. The AM levels were measured by a highly sensitive immunoassay. The AM levels in the CSF of the rats anesthetized with ether (10.7 +/- 0.60 fmol/ml) were significantly higher than those with isoflurane 5.17 +/- 0.70 fmol/ml, P < 0.01), while the plasma level did not differ significantly. The CSF levels of the rats received 2% saline drinking increased to 3 and 4 folds at day 5 and day 7, respectively, while the plasma levels did not differ from controls at both time points. The AM levels in CSF or plasma increased to 1.5 and 3 folds at 1.5 h after intraperitoneal (i.p.) administration of lipopolysaccharide (LPS, 5 mg/kg), reached 6.5 and 30 folds at 6 h, respectively, while no change was observed in the controls. The present findings suggest that AM in the CSF is regulated independently from that in the plasma, the centrally synthesized AM plays and important role in the regulation of the fluid electrolyte homeostasis. Furthermore, the circulatory AM plays an important role in the endotoxin shock.

Adrenomedullin↗

PubMed2004

New isoprenylated flavones, artochamins A--E, and cytotoxic principles from Artocarpus chama.

Five new isoprenylated flavones, artochamins A-E (1-5), together with eight known flavones (6-13), were isolated from the roots of Artocarpus chama. All structures were elucidated by spectroscopic methods. Artonin E (12) showed strong cytotoxicity against 1A9 (ovarian), significant activity against MCF-7 (breast adenocarcinoma), and moderate activity against HCT-8 (ileocecal) and MDA-MB-231 (breast adenocarcinoma) tumor cell lines. Artochamin C (3) was more potent against MCF-7, 1A9, HCT-8, and SK-MEL-2 (melanoma) than A549 (lung carcinoma), KB (epidermoid carcinoma of the nasopharynx), and its drug-resistant (KB-VIN) variant. Artocarpin (6) displayed weak but relatively broad inhibitory effects compared with 3 and 12.

Antineoplastic Agents, Phytogenic↗

PubMed2004

Cost-effectiveness of primary implanted cardioverter defibrillator for sudden death prevention in congestive heart failure.

BACKGROUND: Implanted cardioverter defibrillator (ICD) is expensive but highly effective in preventing sudden death. The value of primary prophylactic ICD in preventing sudden death for congestive heart failure patients (CHF) has not been established. OBJECTIVE: To compare the cost-effectiveness of primary prophylactic ICD vs. standard drug therapy for preventing CHF sudden death. DESIGN: Incremental Cost per Quality-Adjusted Life Year (QALY) using a lifetime decision model. DATA SOURCES: Estimates of cost, utility and probabilities from literature, clinical experts, CMS fee schedule payments, and the Bureau of Labor Statistics. TARGET POPULATION: U.S. CHF patients with NYHA functional Class II and III. TIME HORIZON: Lifetime; future values discounted at 3%. PERSPECTIVE: Societal. RESULTS OF BASE-CASE ANALYSIS: In 2002 prices the discounted lifetime cost is 122,947 dollars with primary prophylactic ICD and 25,223 dollars without ICD; the QALYs gained were 2.9031 and 1.9045 respectively. The incremental cost-effectiveness ratio was 97,861 dollars per QALY saved with prophylactic ICD. RESULTS OF SENSITIVITY ANALYSIS: ICD is not cost-effective under plausible scenarios using 50,000-80,000 dollars per QALY as the cost effectiveness threshold. The cost-effectiveness ratio is quite sensitive to patient utility after ICD implantation, and the proportion of CHF patients experiencing sudden death. CONCLUSIONS: Using a standard cost-effectiveness threshold and plausible parameter ranges, it is unlikely that ICD is cost-effectiveness in preventing CHF sudden death relative to standard drug therapy.

Comorbidity↗

PubMed2004

Localization and in situ quantification of 5-hydroxytryptamine and its receptor in rat submaxillary gland.

5-Hydroxytryptamine (5-HT) and its receptor have been localized and quantified in the submaxillary gland of rats of various ages, using immunohistochemistry, in situ hybridization and in situ quantification. In male rats, the epithelial cells of serous acini, intercalated ducts, secretary tubes and excretory ducts all showed 5-HT and 5-HT receptor (5-HTR) immunoreactivity. Both 5-HT and 5-HTR reactive sites were found in the same cells of adjacent sections. 5-HT1A receptor mRNA hybridized signals could be detected in cytoplasm of these cells. The parasympathetic ganglia cells and endothelial cells of small vessels also showed 5-HT and 5-HTR immunoreactivity in the cytoplasm. However, in female rats, only the epithelial cells in excretory tubes showed 5-HT and 5-HTR immunoreactivity. The immunoreactivity was present in the same cells of adjacent sections. The relative content of 5-HT and its receptor increased during the first 60 postnatal days but remained constant from day 60 to day 90 postnatum. These results suggest that the submaxillary gland of rats possess autocrine 5-HT, which may regulate the function and development of the gland.

Aging↗

PubMed2004

Compressed pattern matching in DNA sequences.

We propose derivative Boyer-Moore (d-BM), a new compressed pattern matching algorithm in DNA sequences. This algorithm is based on the Boyer-Moore method, which is one of the most popular string matching algorithms. In this approach, we compress both DNA sequences and patterns by using two bits to represent each A, T, C, G character. Experiments indicate that this compressed pattern matching algorithm searches long DNA patterns (length > 50) more than 10 times faster than the exact match routine of the software package Agrep, which is known as the fastest pattern matching tool. Moreover, compression of DNA sequences by this method gives a guaranteed space saving of 75%. In part the enhanced speed of the algorithm is due to the increased efficiency of the Boyer-Moore method resulting from an increase in alphabet size from 4 to 256.

Algorithms↗

PubMed2004

Ultrasensitive detection of 1,4-Bis(4-vinylpyridyl)phenylene in a small volume of low refractive index liquid by surface-enhanced Raman scattering-active light waveguide.

This paper reports a novel surface-enhanced Raman scattering (SERS)-active light waveguide method for ultrasensitive detection of a sample dissolved in a small volume of low refractive index liquid. The SERS-active light waveguide demonstrated in this study was constructed via the light-guiding silica capillary. The surface of its inner wall was modified with SERS-active silver nanoparticles that can remarkably enhance Raman signals. The capillary with SERS-active modified layer was filled with the sample solution to form the SERS-active liquid core (LC) fiber. The incident laser beam travels through the waveguide in a totally reflective mode within the fiber wall and penetrates a small distance into the sample solution by the evanescent wave field. The Raman scattering of the analytes adsorbed onto the surface of the SERS-active modified layer can be excited by the laser beam and refracted into the fiber wall. Thus, a sample dissolved in low index liquid, e.g., methanol, can be quantitatively monitored by Raman spectroscopy and detection limit of its concentration is lower than 10(-9) mol/L.

Light↗

PubMed2004

Genome-wide search for type 2 diabetes/impaired glucose homeostasis susceptibility genes in the Chinese: significant linkage to chromosome 6q21-q23 and chromosome 1q21-q24.

This genome-wide search for susceptibility genes to type 2 diabetes/impaired glucose homeostasis (IGH) was performed on a relatively homogeneous Chinese sample with a total number of 257 pedigrees and 385 affected sibpairs. Two regions showed significant linkage to type 2 diabetes/IGH in the Chinese. The region showing linkage to type 2 diabetes/IGH from the entire sample group analysis was located on chromosome 6q21-q23 (128.93 cM, 1-LOD [logarithm of odds] support interval between 124 and 142 cM, according to the Marshfield genetic map), with a maximum likelihood score of 6.23, a nonparametric linkage (all) score of 4.48, and empirical P value <0.001. With a subanalysis based on 101 affected sibpairs with age at diagnosis of type 2 diabetes/IGH <40 years, we detected significant evidence for linkage to chromosome 1q21-q24 (192.1 cM, 1-LOD support interval between 182 and 197 cM), with a maximum likelihood score of 8.91, a nonparametric linkage (all) score of 5.70, and empirical P value <0.001. No interaction was observed between these two regions. Our independent replication of the region on chromosome 1q that has been shown to be linked significantly to type 2 diabetes/IGH in Chinese supports the notion that gene(s) in this region may be universally important in the development of human type 2 diabetes.

Asian People↗