Xiang Ks

Prevalence and clinical characteristics of the mitochondrial tRNA(Leu(UUR)) gene 3243 A to G mutation in familial diabetes mellitus in Chinese population

OBJECTIVE To study the prevalence and clinical characteristics of the A to G mutation at nucleotide 3243 of the mitochondrial tRNA(Leu(UUR)) gene in familial diabetes in Shanghai, Jiangsu and Zhejiang Province of China. METHODS The mt3243 A to G mutation in 770 randomly selected, unrelated probands of diabetic pedigrees were screened by PCR-RFLP technique and PCR-direct sequencing. Genetic and clinical analyses were further performed in the probands and their family members. RESULTS Thirteen diabetic patients (13/770, 1.69%) with mt3243 A to G mutation were detected. Eleven diabetic patients and 8 normal glucose tolerance (NGT) first-degree relatives of these 13 probands were also found bearing the mutation. Seventeen patients were associated with sensory hearing loss. In the 24 patients harboring the mutation, the majority had lower body mass index (BMI), 18 showed typical maternal inheritance, 15 had sensory hearing loss, 13 had insulin resistance and 14 required insulin therapy due to secondary failure to oral hypoglycemic agents. CONCLUSION The mutation of mt3243 A to G in the mitochondrial tRNA(Leu(UUR)) gene is an important cause of diabetes in Shanghai, Jiangsu and Zhejiang Province of China. Mitochondrial gene mutation diabetes (MDM) is clinically characterized by early onset, emaciation, maternal inheritance, sensorineural hearing loss, and lower islet beta cell function, and some have insulin resistance.

Study on the mitochondrial DNA mutations in familial diabetes mellitus in Chinese population

OBJECTIVE To assess the prevalence of mutations or variants of the mitochondrial DNA (mtDNA) in familial diabetes mellitus in Chinese population, and to explore the relationship between mtDNA mutations or variants and diabetes. METHODS Seven hundred and seventy randomly selected, unrelated probands of diabetes pedigrees and 309 controls over 60 years of age with normal glucose tolerance were recruited. PCR-RFLP and PCR-direct sequencing were applied to the screening of mtDNA mutations or variants, including the mutations at nucleotides 3243, 3256 in tRNALeu region, 12258 in tRNASer region, 14709 in tRNAGlu region, 8296, 8344, 8363 in tRNALys region, 3316, 3394, 3426 in ND1 region and 12026 in ND4 region. RESULTS In the diabetic group, 13 (1.69%) had mt3243 A>G mutation, 9(1.17%) had tRNAGlu 14709 T>C variant, 17 (2.21%) carried mt3316 G>A variant, 18 (2.34%) had mt3394 T>C variant, and 28 (3.63%) harbored the 12026 A>G variant. In the control group, the 14709, 3316, 3394, 12026 variants were detected in 5(1.62%), 5(1.62%), 6(1.94%), and 9(2.91%) subjects respectively. The 3256, 8296, 8344, 8363, 3426 and 12258 point mutations were not detected both in the diabetic patients and the controls. In the diabetic group, we found two double mutations, one was A3243G and T3394C, the other was A3243G and A12026G. Except that the A3243G mutation was only observed in the diabetic group, the frequencies of the other variants mentioned above were not statistically different between the diabetic and control groups. Moreover, clinical characteristics such as age of onset, BMI, and insulin resistance index were not different between diabetic patients with and without the variants. CONCLUSION The tRNA (LeuUUR) 3243 A>G mutation may be the major cause of diabetes, representing 1.69% of the familial diabetes mellitus in Chinese. The other variants may be polymorphisms in this population, and the mutations not detected in our studied population may not be common contributors to diabetes mellitus in Chinese.

No association of vascular endothelial growth factor A gene rs9369425 polymorphism with glucose metabolism in Chinese Han population

OBJECTIVE To investigate the relationship between the vascular endothelial growth factor A gene (VEGFA) rs9369425 single nucleotide polymorphism (SNP) and type 2 diabetes in Chinese Han population. METHODS One thousand eight hundred and ninety two type 2 diabetes patients and 1808 controls with normal glucose were recruited in this study. Phenotypes including body mass index, waist, waist hip ratio, plasma glucose and serum insulin levels of blood obtained both at 0 and 120 minute during standard 75-gram glucose oral glucose tolerance tests, were analyzed. Insulin resistance and beta cell function were assessed by homeostasis model assessment (HOMA-IR and HOMA-B). Genotyping was performed by time-of-light mass spectrum using a Sequenom platform. RESULTS The frequencies of minor allele G in the diabetic patients and controls were 10.8% and 11.3% respectively. No significant difference of allele distribution was detected between the cases and controls (P=0.5086). No significant difference (P>0.05) was detected on the association between rs9369425 SNP and clinical phenotypes. CONCLUSION VEGFA rs9369425 was not associated with type 2 diabetes in Chinese Han population. Whether there is association in any other loci in this gene remained to be investigated.