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Association of Genetic Variation of UTS2 Gene with Type2 Diabetes Mellitus and Hypertension

Author: LiHuiZuo
Tutor: SuBenLi
School: Dalian Medical University
Course: Endocrine and metabolic diseases, learning
Keywords: urotensin II SNPs type 2 diabetes mellitus hypertension
CLC: R587.1
Type: Master's thesis
Year: 2011
Downloads: 12
Quote: 0
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Abstract


Objective: Patients with diabetes often accompany hypertension, and patients with hypertension are at high risk for developing diabetes. Along with dyslipidaemia, excess abdominal fat, insulin resistance, the constellation is referred to metabolic syndrome, in which the pathogenesis is elusive even after nearly seventy years of intensive studies. The most current view of pathogenesis is considered to be as a result of genetic and environment interaction. Insulin resistence (IR) and reactive oxygen species injury are supposed to be the common soil of dysmetabolism and cardiovascular diseases. Previous in vitro studies showed UTS2 could directly suppress the isletβcells function, played an important role in the development of insulin resistance. Gene targeting studies showed the locus at 1p36-p32 (where UTS2 gene is located), was associated with type 2 diabete. Therefore, we aimed to investigate the relationship between the polymorphism of site rs228648 in urotensin II (UTS2) gene and the genetic susceptibility to type 2 diabetes mellitus (T2DM), hypertension (HTN) and type 2 diabetes mellitus with hypertension (TH) in Han people, and tried to illustrate if UTS2 would be one of the common SNPs for the development of diabetes and hypertension.Methods: Nine hundred and eight one subjects were enrolled in this study from a health checkup in a university-based hospital in Dalian, China, and 943 subjects were selected for the SNP analysis eliminating 38 subjects who have a tumor or tumor familial history, of whom 81 subjects were diagnosed with type 2 diabetes mellitus but normal blood pressure (TN), 236 subjects with hypertension but normal glucose metabolism (HN), 135 subjects with type 2 diabetes mellitus and hypertension (TH), 181 subjects with impaired glucose regulation but normal blood pressure (IN), 310 normotensive subjects with normal glucose regulation, (normal control group (NCG). after undertaking 75gOGTT and determination of fasting and 2h plasma glucose. Insulin was determined with radioimmunoassay and biochemical indexes were analyzed with automatic analyzer in the central lab of the hospital. Peripheral white cell DNA was extracted by phenol-chloroform extraction. SNP at UTS2 gene positions rs228648 was analyzed using polymerase chain reaction and ligase detection reaction (LDR) analysis. Then we analyzed the relationship between the polymorphism of site rs228648 in UTS2 gene and the genetic susceptibility to T2DM, HTN and TH. All statistical analyses were performed using the SPSS software (version17.0). A P value of less than 0.05 was considered statistically significant.Results:1. The distribution of rs228648 frequency was consistent with HWE in the control and study groups. No difference was found in genotype frequencies between the control and study groups.2. After adjusting age and gender, Logistic multifactor analysis showed rs228648 genotypic distribution was similar between TN and NCG, between HN and NCG. between TH and NCG, and between IN and NCG (P>0.05).3. The associations between genotypes and phenotypes in NCG were analyzed. Subjects with AA genotype had higher TC level than subjects with GG genotype (5.8 vs. 5.4 mmol/L, P<0.05); the GA genotype carriers had lower PPG level than subjects with GG genotype (5.9 vs. 6.4 mmol/L, P<0.05) and higher FPI level than subjects with GG or AA genotypes (7.7 vs. 6.6 or 5.8 mU/L, P<0.05), and higher HOMA-IR value than subjects with AA genotypes (1.6 vs. 1.3, P<0.05), and higher HOMA-βvalue than subjects with GG or AA genotypes (124.3 vs. 96.4 or 93.4; P<0.05). No association of genotype with phenotype of HOMA-IR, HOMA-βand ISI was found in group IN (P>0.05).Conclusions: The present study did not found the UTS2 gene was associated with the risk of T2DM, HTN, TH in a Han Chinese sample. The gene mutation might be related to dyslipidemia,β-cell function, and insulin release.

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CLC: > Medicine, health > Internal Medicine > Endocrine diseases and metabolic diseases > Islet disease > Diabetes
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