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. 2017 Sep 29;12(9):e0185529.
doi: 10.1371/journal.pone.0185529. eCollection 2017.

Associations of melatonin receptor gene polymorphisms with Graves' disease

Jiunn-Diann Lin  1   2   3 , Shun-Fa Yang  4   5 , Yuan-Hung Wang  1   6 , Wen-Fang Fang  7 , Ying-Chin Lin  7 , Bing-Chun Liou  1 , Yuh-Feng Lin  1   8 , Kam-Tsun Tang  9 , Chao-Wen Cheng  1
Affiliations

Associations of melatonin receptor gene polymorphisms with Graves' disease

Jiunn-Diann Lin et al. PLoS One. .

Abstract

Background: Melatonin plays an important role in immunity and has been linked to autoimmune diseases. Possible associations of single-nucleotide polymorphisms (SNPs) of melatonin receptor type 1A (MTNR1A) and 1B (MTNR1B), with autoimmune thyroid disease in an ethnic Chinese (i.e., Taiwanese) population were examined.

Materials and methods: Totally, 83 Hashimoto's thyroiditis patients, 319 Graves' disease (GD), and 369 controls were recruited. Three SNPs (rs6553010, rs13140012, and rs2119882) of MTNR1A and three SNPs (rs1387153, rs10830963, and rs1562444) of MTNR1B were genotyped.

Results: There were a reduced frequency of the C allele of rs2119882 and a reduced percentage of the CC+CT genotype in the GD group compared to the control group (p = 0.039, odds ratio (OR) = 0.79, 95% confidence interval (CI) = 0.63~0.99, and p = 0.032, OR = 0.72, 95% CI = 0.53~0.97, respectively). There was a significant difference in the percentage of the AT haplotype of the combination of rs13140012 and rs2119882 between the GD and control groups (p = 0.010, OR = 1.34, 95% CI = 1.07~1.67). In addition, there were significant associations of anti-thyroid peroxidase antibody titers with rs13140012 and rs2119882, and the AATT genotype of the combination of rs13140012 and rs2119882 (p = 0.003, 0.003, and 0.004, respectively). There were no significant associations of SNPs and possible haplotypes of MTNR1B with susceptibility to GD.

Conclusions: Genetic variants of rs2119882 of MTNR1A and the AT haplotype of the combination of rs2119882 and rs13140012 were associated with GD susceptibility in an ethnic Chinese population. The results support the involvement of the melatonin pathway in the pathogenesis of GD.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1
Pairwise linkage disequilibrium patterns of melatonin receptor type 1A (panel A) and type 1B (panel B).
Fig 2
Fig 2. Anti-thyroid peroxidase antibody (anti-TPO Ab) titers at the baseline in different genotypes of rs6553010, rs13140012, and rs2119882, and the combined genotype of rs13140012 and rs2119882 in patients with Graves’ disease.
Low anti-TPO, low anti-TPO Ab titer (≤1:1600); high anti-TPO, high anti-TPO Ab titer (1:6400~1:25,600 and >1:25,600); the number in the column indicates the frequency of the genotype.
See this image and copyright information in PMC

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