Genetic analysis of thyroid peroxidase (TPO) gene in patients whose hypothyroidism was found in adulthood in West Bengal, India

被引:18
作者
Balmiki, Nisha [1 ]
Bankura, Biswabandhu [1 ]
Guria, Srikanta [2 ]
Das, Tapas Kumar [3 ]
Pattanayak, Arup Kumar [1 ]
Sinha, Anirban [4 ]
Chakrabarti, Sudipta [5 ]
Chowdhury, Subhankar [4 ]
Das, Madhusudan [1 ]
机构
[1] Univ Calcutta, Dept Zool, Kolkata 700019, India
[2] Darjeeling Govt Coll, Post Grad Dept Zool, Parasitol & Med Entomol Lab, Darjeeling 734101, India
[3] Bagnan Rural Hosp, Bagnan 711303, Howrah, India
[4] Inst Post Grad Med Educ & Res, Dept Endocrinol, Kolkata 700020, India
[5] Inst Life Sci, Bhubaneswar, Orissa, India
关键词
Hypothyroidism; Thyroid peroxidase gene; Single nucleotide polymorphisms; Association; Risk allele; IODIDE ORGANIFICATION DEFECT; CONGENITAL HYPOTHYROIDISM; MOLECULAR ANALYSIS; MUTATION ANALYSIS; PENDRED-SYNDROME; IDENTIFICATION; CHILDREN;
D O I
10.1507/endocrj.EJ13-0237
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Recent research has revealed that genetic defects due to mutation in the Thyroid Peroxidase (TPO) gene can lead to thyroid dysfunction in the population. We aimed to study the association between genetic defects in TPO gene and patients with hypothyroidism found in adult age. Two hundred consecutive treatment naive hypothyroid patients (age >= 18 years) (cases) who were negative for anti TPO antibody and their corresponding sex and age matched two hundred normal individuals (controls) were enrolled. The 17 exonic regions of the TPO gene were amplified and sequenced directly. We identified 6 different previously known single nucleotide polymorphisms (SNPs) and 2 novel deletions in TPO gene. Two of the six SNPs revealed a significant association with hypothyroidism; Thr725Pro (rs732609) and Asp666Asp (rs1126797). The c.2173C allele of the Thr725Pro in TPO showed a significant association among hypothyroid patients compared to controls (p = 0.01; Odds ratio=1.45; 95% CI: 1.09-1.92) suggesting it to be a potential risk allele toward disease predisposition. Analysis of genotype frequencies of the polymorphism between the two groups demonstrated CC as a potential risk genotype (p = 0.006; Odds ratio=1.95; 95% CI: 1.2-3.15) for the disease while another SNP Asp666Asp (c.1998T allele) showed protectiveness towards the disease (p = 0.006; Odds ratio = 0.67; 95%CI: 0.50-0.89). To our knowledge, this is first study reporting the role of TPO gene with hypothyroidism in a population of Asian Indian origin. The study threw up the possibility of TPO gene polymorphisms as a possible pathogenetic mechanism of hypothyroidism.
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收藏
页码:289 / 296
页数:8
相关论文
共 31 条
[1]   IDENTIFICATION OF A MUTATION IN THE CODING SEQUENCE OF THE HUMAN THYROID PEROXIDASE GENE CAUSING CONGENITAL GOITER [J].
ABRAMOWICZ, MJ ;
TARGOVNIK, HM ;
VARELA, V ;
COCHAUX, P ;
KRAWIEC, L ;
PISAREV, MA ;
PROPATO, FVE ;
JUVENAL, G ;
CHESTER, HA ;
VASSART, G .
JOURNAL OF CLINICAL INVESTIGATION, 1992, 90 (04) :1200-1204
[2]   AN ANALYSIS OF THE STRUCTURE AND ANTIGENICITY OF DIFFERENT FORMS OF HUMAN THYROID PEROXIDASE [J].
BAKER, JR ;
ARSCOTT, P ;
JOHNSON, J .
THYROID, 1994, 4 (02) :173-178
[3]   Two decades of screening for congenital hypothyroidism in the Netherlands: TPO gene mutations in total iodide organification defects (an update) [J].
Bakker, B ;
Bikker, H ;
Vulsma, T ;
De Randamie, JSE ;
Wiedijk, BM ;
De Vijlder, JJM .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2000, 85 (10) :3708-3712
[4]  
Bavadam L, 2006, FRONTLINE, V23, P1
[5]   IDENTIFICATION OF 5 NOVEL INACTIVATING MUTATIONS IN THE HUMAN THYROID PEROXIDASE GENE BY DENATURING GRADIENT GEL-ELECTROPHORESIS [J].
BIKKER, H ;
VULSMA, T ;
BAAS, F ;
DEVIJLDER, JJM .
HUMAN MUTATION, 1995, 6 (01) :9-16
[6]   Congenital hypothyroidism caused by a premature termination signal in exon 10 of the human thyroid peroxidase gene [J].
Bikker, H ;
Waelkens, JJJ ;
Bravenboer, B ;
deVijlder, JJM .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1996, 81 (06) :2076-2079
[7]   Molecular analysis of mutated thyroid peroxidase detected in patients with total iodide organification defects [J].
Bikker, H ;
Baas, F ;
DeVijlder, JJM .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1997, 82 (02) :649-653
[8]   Molecular analysis of the PDS gene in Pendred syndrome (sensorineural hearing loss and goitre) [J].
Coyle, B ;
Reardon, W ;
Herbrick, JA ;
Tsui, LC ;
Gausden, E ;
Lee, J ;
Coffey, R ;
Grueters, A ;
Grossman, A ;
Phelps, PD ;
Luxon, L ;
Kendall-Taylor, P ;
Scherer, SW ;
Trembath, RC .
HUMAN MOLECULAR GENETICS, 1998, 7 (07) :1105-1112
[9]   Cloning and characterization of the thyroid iodide transporter [J].
Dai, G ;
Levy, O ;
Carrasco, N .
NATURE, 1996, 379 (6564) :458-460
[10]   Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS) [J].
Everett, LA ;
Glaser, B ;
Beck, JC ;
Idol, JR ;
Buchs, A ;
Heyman, M ;
Adawi, F ;
Hazani, E ;
Nassir, E ;
Baxevanis, AD ;
Sheffield, VC ;
Green, ED .
NATURE GENETICS, 1997, 17 (04) :411-422