ABSTRACT
Background@#Vascular complications are the major morbid consequences of type 2 diabetes mellitus (T2DM). The transcription factor 7-like 2 (TCF7L2), potassium voltage-gated channel subfamily Q member 1 (KCNQ1), and inwardly-rectifying potassium channel, subfamily J, member 11 gene (KCNJ11) are common T2DM susceptibility genes in various populations. However, the associations between polymorphisms in these genes and diabetic complications are controversial. This study aimed to investigate the effects of combined gene-polymorphisms within TCF7L2, KCNQ1, and KCNJ11 on vascular complications in Thai subjects with T2DM. @*Methods@#We conducted a case-control study comprising 960 T2DM patients and 740 non-diabetes controls. Single nucleotide polymorphisms in TCF7L2, KCNQ1, and KCNJ11 were genotyped and evaluated for their association with diabetic vascular complications. @*Results@#The gene variants TCF7L2 rs290487-T, KCNQ1 rs2237892-C, and KCNQ1 rs2237897-C were associated with increased risk of T2DM. TCF7L2 rs7903146-C, TCF7L2 rs290487-C, KCNQ1 rs2237892-T, and KCNQ1 rs2237897-T revealed an association with hypertension. The specific combination of risk-alleles that have effects on T2DM and hypertension, TCF7L2 rs7903146-C, KCNQ1 rs2237892-C, and KCNQ1 rs2237897-T, as genetic risk score (GRS), pronounced significant association with coronary artery disease (CAD), cumulative nephropathy and CAD, and cumulative microvascular and macrovascular complications (respective odds ratios [ORs] with 95% confidence interval [95% CI], comparing between GRS 2–3 and GRS 5–6, were 7.31 [2.03 to 26.35], 3.92 [1.75 to 8.76], and 2.33 [1.13 to 4.79]). @*Conclusion@#This study demonstrated, for the first time, the effect conferred by specific combined genetic variants in TCF7L2 and KCNQ1 on diabetic vascular complications, predominantly with nephropathy and CAD. Such a specific pattern of gene variant combination may implicate in the progression of T2DM and life-threatening vascular complications.
ABSTRACT
Background@#Vascular complications are the major morbid consequences of type 2 diabetes mellitus (T2DM). The transcription factor 7-like 2 (TCF7L2), potassium voltage-gated channel subfamily Q member 1 (KCNQ1), and inwardly-rectifying potassium channel, subfamily J, member 11 gene (KCNJ11) are common T2DM susceptibility genes in various populations. However, the associations between polymorphisms in these genes and diabetic complications are controversial. This study aimed to investigate the effects of combined gene-polymorphisms within TCF7L2, KCNQ1, and KCNJ11 on vascular complications in Thai subjects with T2DM. @*Methods@#We conducted a case-control study comprising 960 T2DM patients and 740 non-diabetes controls. Single nucleotide polymorphisms in TCF7L2, KCNQ1, and KCNJ11 were genotyped and evaluated for their association with diabetic vascular complications. @*Results@#The gene variants TCF7L2 rs290487-T, KCNQ1 rs2237892-C, and KCNQ1 rs2237897-C were associated with increased risk of T2DM. TCF7L2 rs7903146-C, TCF7L2 rs290487-C, KCNQ1 rs2237892-T, and KCNQ1 rs2237897-T revealed an association with hypertension. The specific combination of risk-alleles that have effects on T2DM and hypertension, TCF7L2 rs7903146-C, KCNQ1 rs2237892-C, and KCNQ1 rs2237897-T, as genetic risk score (GRS), pronounced significant association with coronary artery disease (CAD), cumulative nephropathy and CAD, and cumulative microvascular and macrovascular complications (respective odds ratios [ORs] with 95% confidence interval [95% CI], comparing between GRS 2–3 and GRS 5–6, were 7.31 [2.03 to 26.35], 3.92 [1.75 to 8.76], and 2.33 [1.13 to 4.79]). @*Conclusion@#This study demonstrated, for the first time, the effect conferred by specific combined genetic variants in TCF7L2 and KCNQ1 on diabetic vascular complications, predominantly with nephropathy and CAD. Such a specific pattern of gene variant combination may implicate in the progression of T2DM and life-threatening vascular complications.
ABSTRACT
The reference interval of serum Y-glutamyltransferase for Thai people was carried out in 103 healthy men and 98 healthy woman. The enzyme activity ranged from 2.13 to 40.21 IU/L and 0.18 to 32.34 IU/L for men and women respectively. No singnificant difference of the enzyme activity between sexes was demonstrated ( p \> 0.05 ). However, the enzyme activity of subjects in both sexes which aged below 20 years showed a less activity and significant difference than those aged above 20 years. ( p \< 0.05 )
ABSTRACT
Platelets play a critical role in atherothrombosis and platelet membrane glycoproteins are essential for the activation processes. A numbers of genetic polymorphisms of platelet membrane glycoproteins have been identified and some of them may predispose to thromboembolic events. Glycoprotein IIb/IIIa (GPIIb/IIIa) is the most abundant platelet receptors consisting of 2 subunits, GPIIb and GPIIIa. The GPIIIa Leu33Pro polymorphism has previously been reported to be associated with coronary artery disease (CAD) in several racial groups but has not been studied in Laos. Since CAD is becoming one of the high priority health problems in Lao People’s Democratic Republic (PDR), study of the prevalence of the GPIIIa Leu33Pro polymorphism may provide the fundamental information for future evaluation of the association with the risk of CAD in this population. Two hundred unrelated subjects attended to Mahosod hospital, Vientiane, Lao PDR, for health check-up were recruited in this study, and divided into 2 groups composed of 100 individuals in each group with normal and abnormal serum lipids. All subjects had no history and clinical signs of arterial or venous thrombosis as well as a bleeding tendency. The GPIIIa Leu33Pro polymorphism was determined in genomic DNA extracted from leukocytes, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The results demonstrated genotype frequencies of Leu/Leu and Leu/Pro in normolipidemia and dyslipidemia were 96.0 \& 99.0 % and 4.0 \& 1.0 %, respectively, whilst the respective allele frequencies of Leu and Pro were 0.98 \& 0.99 and 0.02 \& 0.01. There were no significant differences of the genotype and allele frequencies between both groups (p \> 0.05). The homozygous Pro/Pro was not found in both groups. This is the first report of the genotype distribution of the GPIIIa Leu33Pro polymorphism in Lao PDR which showed similar prevalence as in Asians but lower than those in Caucasian populations.
ABSTRACT
Apolipoprotein E (apoE) is a constituent on lipoprotein surface and plays an important role in lipid metabolism. There are three common isoforms of human apoE, designed apoE2, apoE3 and apoE4 that are coded by three polymorphic alleles of the APOE genes, e2, e3 and e4. Polymorphism of APOE influences the blood lipid concentration and may contribute to susceptibility to dyslipidemia. The present study was therefore to investigate the role of APOE polymorphism on blood lipid levels in Thai individuals. A total of 121 normolipidemic and 125 dyslipidemic subjects were recruited. DNA was isolated from peripheral blood leukocytes and APOE genotypes were determined by PCR-RFLP. Allele frequencies of e2, e3 and e4 were 9.3%, 77.8% and 12.8%, respectively. The respective prevalence of APOE genotypes for e2/e2, e3/e3, e4/e4, e2/e3, e2/e4 and e3/e4 were 1.2%, 62.2%, 0.8%, 11.8%, 4.5% and 19.5%. The frequencies of APOE allele and genotype of both groups as well as the relation of APOE genotypes to the risk of dyslipidemia were not significantly different. The elevation of some lipid parameters observed in male subjects and the higher level of lipid profile in dyslipidemic group may be due to other factors and gene polymorphisms.