Association of Type II 5′ Monodeiodinase Thr92Ala Single Nucleotide Gene Polymorphism and Circulating Thyroid Hormones Among Type 2 Diabetes Mellitus Patients

被引：9

作者：

Yalakanti D. ^{[1
]}

Dolia P.B. ^{[1
]}

机构：

[1] Institute of Biochemistry, Madras Medical College & RGGGH, Chennai, 600003, Tamilnadu

来源：

Indian Journal of Clinical Biochemistry | 2016年 / 31卷 / 2期

关键词：

DIO2; Thr92Ala; Paraoxonase; Thyroid hormones; Type 2 diabetes mellitus; Type II 5′ monodeiodinase;

D O I：

10.1007/s12291-015-0518-9

中图分类号：

学科分类号：

摘要：

Diabetes mellitus and thyroid disorders are common endocrinopathies, which often occur parallel. Dyslipidemia is very common in both of these conditions. The development of hypothyroidism is well-known in type 1 diabetics, but it was not distinctly understood in type 2 diabetics. Thus we tried to examine the association between type II deiodinase (D2 or DIO2) Thr92Ala single nucleotide gene polymorphism and thyroid function among type 2 diabetes mellitus patients. A total of 130 type 2 diabetics were screened and genotyped for DIO2 Thr92Ala polymorphism. Fasting plasma glucose, Glycosylated haemoglobin, lipid and thyroid profiles, malondialdehyde (MDA) and paraoxonase were estimated according to standard procedures. A significant altered level of thyroid hormones (TH’s) was found in Ala/Ala genotype when compared with Thr/Thr or Thr/Ala genotype. DIO2 and T3:T4 ratio significantly decreased, whereas total T4 and thyroid stimulating hormone levels significantly elevated among Ala/Ala genotype (131 ± 30 ng/ml; 0.12 ± 0.05; 7.17 ± 2.05 µg/dl; 4.77 ± 3.1 µIU/ml, respectively) when compared with Thr/Thr + Thr/Ala genotypes (176 ± 33 ng/ml; 0.21 ± 0.05; 5.21 ± 1.1 µg/dl; 2.59 ± 1.61 µIU/ml respectively). Moreover, D2 levels were significantly negatively correlated with TH’s levels except total T4 among Ala/Ala genotypes. All the patients were having a poor glycemic control, and their glycemic status was positively correlating with MDA levels. On the other hand, serum paraoxonase activity decreased among Ala/Ala genotype (104 ± 21 vs. 118 ± 18 nmol/min/ml). In conclusion, DIO2 Ala92 homozygous variant found to be associated with altered levels of DIO2, Thyroid profile and paraoxonase. Hence, we recommend to do detail study of genetic factors related to thyroid function and prevent additional diabetic complications. © 2015, Association of Clinical Biochemists of India.

引用

页码：152 / 161

页数：9

共 34 条

[1]

Duntas L.H., Thyroid disease and lipids, Thyroid, 12, pp. 287-293, (2002)

[2]

Polikar R., Burger A.G., Scherrer U., Nicod P., The thyroid and the heart, Circulation, 87, 5, pp. 1435-1441, (1993)

[3]

Braverman L.E., Ingbar S.H., Sterling K., Conversion of T4 to T3 in athyreotic subjects, J Clin Invest., 49, pp. 855-864, (1970)

[4]

Antonio C., Salvatore D., Gereben B., Berry M.J., Larsen P.R., Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases, Endocr Rev., 23, 1, pp. 38-89, (2002)

[5]

Collins F.S., Brooks L.D., Chakravarti A., A DNA polymorphism discovery resource for research on human genetic variabtion, Genome Res., 8, pp. 1229-1231, (1998)

[6]

Brookes A.J., The essence of SNP’s, Gene, 234, pp. 177-186, (1999)

[7]

Dora A.J., Machado W.E., Rheinheimer J., Crispim D., Maia A.L., Association of the type 2 deiodinase Thr92Ala polymorphism with type 2 diabetes: case–control study and meta-analysis, Eur J Endocrinol., 163, pp. 427-434, (2010)

[8]

Canani L.H., Capp C., Dora J.M., Meyer E.L., Wagner M.S., Harney J.W., Et al., The type 2 deiodinase A/G (Thr92Ala) polymorphism is associated with decreased enzyme velocity and increased insulin resistance in patients with type 2 diabetes mellitus, J Clin Endocrinol Metab., 90, pp. 3472-3478, (2005)

[9]

Meulenbelt I., Min J.L., Bos S., Riyazi N., Houwing-Duistermaat J.J., Van Der Wijk H.J., Et al., Identification of DIO2 as a new susceptibility locus for symptomatic osteoarthritis, Hum Mol Genet., 17, pp. 1867-1875, (2008)

[10]

Gumieniak O., Perlstein T.S., Williams J.S., Hopkins P.N., Brown N.J., Raby B.A., Et al., Ala92 type 2 deiodinase allele increases risk for the development of hypertension, Hypertension, 49, pp. 461-466, (2007)

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