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Biomedical subjects

K Xiang

Publications and source records attributed to K Xiang.

At least 37 records · Page 2Linked to original sources
PubMed1996

Glucokinase gene variants in Chinese subjects with the common form of NIDDM.

OBJECTIVE: To determine whether mutation of the coding or junction region of glucokinase gene (GCK) is also the pathogenic cause of the common form of non-insulin-dependent diabetes mellitus (NIDDM) in Chinese. METHODS: Single strand conformation polymorphism (SSCP) analysis was performed after the 12 exons and junction regions of GCK of each subject studied were separately amplified with polymerase chain reaction (PCR). The molecular scanning was carried out in 30 Chinese subjects with common form NIDDM having the age of onset at or before 45 years, and/or with positive family history of diabetes mellitus (NIDDM-A group). Further screening of the mutation/variation found was conducted in 56 NIDDM subjects (NIDDM-B group) and 134 non-diabetes subjects (ND group) in order to define their frequencies. RESULTS: No mutation was found by molecular scanning in coding or junction region of GCK in NIDDM-A group. A variant of intron I b was detected in GCK of NIDDM subjects, especially in those with early age of onset and/or with positive family history of diabetes. Significant difference in incidences was found between ND group and NIDDM-A+B group (0% vs 4.7%, Fisher exact P = 0.022). CONCLUSIONS: (1) Mutation of coding and junction regions of GCK is not the main pathogenic factor of common form NIDDM in Chinese subjects. (2) A variant of GCK intron I b may be found in NIDDM in Chinese, especially in those with early age of onset and/or with positive family history of diabetes. Its role in the expression of GCK remain to be elucidated.

Adult↗
PubMed1995

[Genetic diagnosis of a subtype diabetes mellitus with mitochondrial tRNA Leu(UUR) gene mutation].

The A-G point mutation of mitochondrial tRNALeu(UUR) gene at nucleotide 3243 caused clinical NIDDM in combination with or without deafness and was inherited through maternal transmission. An ApaI restriction site was resulted by this mutation, which could be detected by polymerase chain reaction (PCR) with ApaI digestion and be used in clinical genetic diagnosis. The first Chinese family with this mutation found through our screening of NIDDM patients was reported. Genetic diagnosis was done in 12 of 15 members in this three-generation pedigree. Positive results (present of ApaI restriction site) were observed in all 5 NIDDM patients (four with deafness). In 6 of 7 non-diabetic members, negative genetic diagnosis was obtained. The presymptomatic diagnosis of this disease was made in a 13-year old non-diabetic boy with positive genetic diagnosis in conjunction with the maternal segregation pattern of the mutation in this family. The finding of this disease in Chinese provides firm evidence of genetic heterogeneity in Chinese NIDDM. The techniques of the genetic diagnosis of this disease can be used in clinical laboratory, which indicates that in the diagnosis of NIDDN, the molecular etiologic level can be reached in daily clinical practice.

Adolescent↗
PubMed1995

Relationship of LDLR gene polymorphism and NIDDM in Chinese.

Genomic DNA was extracted from peripheral blood lymphocytes of 105 healthy and 75 NIDDM Chinese subjects. The fragment located in exon 13 of the low density lipoprotein receptor (LDLR) gene was amplified by polymerase chain reaction (PCR), and digested with restriction enzyme HincII. LDL, TC and TG levels were measured in all subjects. Investigations were conducted to explore the correlation between the HincII RFLP of LDLR gene and NIDDM in the Chinese population. The results showed that no significant correlation existed between this RFLP locus and NIDDM. Marked differences were found, however, between the genotype distribution of low LDL level subgroups of NIDDM patients and normal controls. It was inferred that the H1 allele might be associated with high blood cholesterol levels, and the H2 allele with low cholesterol levels. Disturbances of lipid metabolism occur frequently in diabetes mellitus. This study suggested that differences in LDLR genotypes may affect the phenotypes of lipid metabolism.

Adult↗
PubMed1995

The population association of glucokinase gene with type 2 (noninsulin-dependent) diabetes mellitus in Chinese.

The association of gluckinase (GCK) gene with type 2 (non-insulin-dependent) diabetes mellitus was investigated in 168 Chinese subjects (85 unrelated type 2 diabetics and 83 non-diabetic controls). The microsatellite polymorphism marker, GCK-5', was amplified with polymerase chain reaction. Four alleles were observed in Chinese population with length varying from 137bp to 143bp and the most common one being the 139bp allele 3. In comparison with non-diabetics, allele 4 was significantly increased in type 2 diabetes (10% versus 38, respectively; X2 = 6.773, P = 0.009); genotype 44 and 4X (X denotes any allele other than allele 4) were significantly increased in type 2 diabetes (16% versus 6% respectively; X2 = 6.439, P = 0.011). The frequency difference was also shown in overweight/obese subgroup comparison (X2 = 7.718, P = 0.021), but not in lean/normal-weight subgroup comparison. No differences of age of onset and frequency of positive family history were observed between type 2 diabetic patients with genotype 44 or 4X and those with XX. The risk for type 2 diabetes in Chinese with genotype 44 or 4X was about 3.5 times higher than in Chinese with genotype XX. Therefore, GCK gene was associated with Chinese type 2 diabetes.

Adult↗
PubMed1993

Human hexokinase II: localization of the polymorphic gene to chromosome 2.

Type 2 (non-insulin-dependent) diabetes mellitus is characterized by decreased levels of glucose 6-phosphate in skeletal muscle. It has been suggested that the lower concentrations of glucose 6-phosphate contribute to the defect in glucose metabolism noted in muscle tissue of subjects with Type 2 diabetes or subjects at increased risk of developing Type 2 diabetes. Lower levels of glucose 6-phosphate could be due to a defect in glucose uptake, or phosphorylation, or both. Hexokinase II is the isozyme of hexokinase that is expressed in skeletal muscle and is responsible for catalysing the phosphorylation of glucose in this tissue. The recent demonstration that mutations in another member of this family of glucose phosphorylating enzymes, glucokinase, can lead to the development of Type 2 diabetes prompted us to begin to examine the possible role of hexokinase II in the development of this genetically heterogeneous disorder. As a first step, we have cloned the human hexokinase II gene (HK2) and mapped it to human chromosome 2, band p13.1, by fluorescence in situ hybridization to metaphase chromosomes. In addition, we have identified and characterized a simple tandem repeat DNA polymorphism in HK2 and used this DNA polymorphism to localize this gene within the genetic linkage map of chromosome 2.

Alleles↗
PubMed1992

Human pancreatic beta-cell glucokinase: cDNA sequence and localization of the polymorphic gene to chromosome 7, band p 13.

The glucose phosphorylating enzyme glucokinase plays an important role in the regulation of glucose homeostasis. Studies in rodents indicate that pancreatic Beta cells and hepatocytes express different isoforms of this protein as a consequence of the presence of tissue-specific promoters and exon 1 sequences which are spliced to a shared group of nine exons which encode most of the mRNA and protein. Here, we report the isolation and characterization of cDNA clones encoding human Beta-cell glucokinase. The sequence of human Beta-cell glucokinase shows 97% amino acid identity with that of the cognate rat protein. We also mapped the human glucokinase gene to the short arm of chromosome 7 by analysing its segregation in a panel of reduced human-mouse somatic cell hybrids. In situ hybridization to metaphase chromosomes confirmed the localization of the human glucokinase gene to chromosome 7 and indicated that it was in band p 13. A microsatellite DNA polymorphism that can be typed using the polymerase chain reaction was identified upstream of exon 1 a, the Beta-cell specific first exon. The glucokinase cDNA clone and highly informative DNA polymorphism will be useful for examining the role of this gene in the pathogenesis of diabetes mellitus.

Amino Acid Sequence↗