Coexistence of aldose reductase gene and endothelial nitric oxide synthase polymorphisms associates with diabetic nephropathy / 中国组织工程研究
Chinese Journal of Tissue Engineering Research
;
(53): 6893-6896, 2007.
Article
in Chinese
| WPRIM
| ID: wpr-407670
ABSTRACT
BACKGROUND:
It has been demonstrated that the C-106T polymorphism at promotor region of aldose reductase gene and GLU298ASP (894G→T) polymorphism at exon 7 of endothelial nitric oxide synthase (eNOS) gene are associated with diabetic nephropathy, it should be further studied wnether the risk for diabetic nephropathy will increase when the above polymorphic sites coexist.OBJECTIVE:
To investigate the association between the coexistence of the polymorphisms of both the C-106T at promotor region of aldose reductase gene and GLU298ASP (894G→T) at axon 7 of eNOS gene in chromosome 7q35 region and the genesis of diabetic nephropathy in northern Chinese Hah people.DESIGN:
A case-controlled, comparative observation.SETTING:
Department of Endocrinology, the Affiliated Hospital of Medical College, Qingdao University.PARTTCIPANTS; Totally 139 inpatients with type 2 diabetes mellitus were selected from the Department of Endocrinology, the Affiliated Hospital of Medical College, Qingdao University from November 2002 to April 2005,including 54 males and 85 females, (64±8) years of age. Inclusive criteria Accorded with the standards of diabetic diagnosis and classification by WHO in 1999. According to the 24-hour urinary albumin excretion rate (UAER), they were divided into diabetic nephropathy group (n =61) and non-diabetic nephropathy group (n =78). Meanwhile, 63 healthy controls were selected as the control group, including 24 males and 39 females, 50-78 years of age. All the enrolled subjects were Han people. Informed contents were obtained from all the subjects.METHODS:
The genotypes and alleles of polymorphisms of GLU298ASP(894G→T) at exon 7 of eNOS gene and C-106T at promotor region of aldose reductase gene were detected by polymerase chain reaction restriction-fragment length polymorphism technique (PCR-RFLP), DNA sequencing technique and agarose gel electrophoresis separation technique.Then the frequency of genotypes and alleles were compared.MAIN OUTCOMEMEASURES:
① Polymorphisms of eNOS gene and aldose reductase gene; ② Results of the multivariant stepwise regression analysis of risk factors for diabetic nephropathy; ③ Polymorphisms of aldose reductase C-106T and eNOS 894G→T and the relative risk of diabetic nephropathy.RESULTS:
All the 139 patients with type 2 diabetes mellitus and 63 healthy adults were involved in the analysis of results. ① The frequencies of the T allele and TG genotype at exon 7 894G→T polymorphic site of eNOS gene in the diabetic nephropathy group were significantly higher than those in the non-diabetic nephropathy group and control group (χ2=8.261, 19.629, P < 0.05). ② The frequencies of the T allele and CT genotype at promotor region of aldose reductase gene in the diabetic nephropathy group were significantly higher than those in the non-diabetic nephropathy group and control group (χ2=6.343, 8.940, P < 0.05, 0.01). ③ After associated analysis on the above gene polymorphisms, it was found that the frequency of TG/CT genotype in the diabetic nephropathy group were significantly higher than that in the non-diabetic nephropathy group and control group (χ2=6.972, P < 0.01); whereas the frequency of GG/CC genotype was significantly lower than that in the non-diabetic nephropathy group and control group (χ2=13.304, P < 0.05). ④Glycosylated hemoglobin (GHbA1c), systolic blood pressure, total cholesterol, polymorphisms of 894G→T at exon 7 of eNOS gene and C-106T at promotor region of aldose reductase gene were all the independent risk factors for diabetic nephropathy (Wald =5.627, 4.92, P < 0.05). ⑤ GG/GC genotype might be the protective genotype for diabetic nephropathy (OR=0.25, P < 0.01); The risk for diabetic nephropathy in the carrier of GG/CT or TG/CC genotype increased by 2.3 times and risk for diabetic nephropathy in the carrier of TG/CT genotype increased by 4.8 times.CONCLUSION:
The coexistence of polymorphisms of 894G→T at exon 7 of eNOS gene and C-106T at promotor region of aldose reductase gene can increase the risk of diabetic nephropathy in patients with type 2 diabetes mellitus. And the TG/CT haplotype formed by the coexistence of polymorphism of these two genes is probably the predisposing genotype for diabetic nephropathy.
Full text:
Available
Index:
WPRIM (Western Pacific)
Type of study:
Etiology study
/
Practice guideline
Language:
Chinese
Journal:
Chinese Journal of Tissue Engineering Research
Year:
2007
Type:
Article
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