Association between TPO Asn698Thr and Thr725Pro gene polymorphisms and serum anti-TPO levels in Iranian patients with subclinical hypothyroidism

Abstract

ObJeCTIVe: Subclinical hypothyroidism (SCH) is defined as high levels of TSH in the presence of normal levels of serum FT4. Since thyroid peroxidase (TPO) plays a key role in thyroid hormone synthesis, variations in the TPO gene can change the enzyme structure and result in the production of anti-TPO antibodies. The aim of this study was to examine the relationship between the Asn698Thr (A2095C) and Thr725Pro (A2173C) polymorphisms of the TPO gene and anti-TPO levels in patients with SCH. DESIGN: In this study, 150 individuals (75 cases and 75 controls), aged 19-75 years, were selected randomly by a clinician. The thyroid function tests included were FT3, FT4, TSH and anti-TPO antibodies using elISA. The TPO gene polymorphisms were examined by PCR-RFlP. ReSUlTS: Anti-TPO levels in the experimental group was significantly increased (P=0.020). The A2095C genotype frequency in the experimental and control groups were 37.3% vs 34.7% for the AA healthy genotype, 20% vs 46.7% for AC and 42.7% vs 18.6% for CC, respectively (P=0.001). The A2173C genotype frequency in the experimental and control groups were 22.6% vs 68% for healthy AA, 40% vs 25.3% for AC and 37.4% vs 6.7% for CC, respectively (P <0.001). The increased anti-TPO antibodies were significantly associated with the A2173C polymorphism (P=0.035). The findings showed that the chance (odds ratio) of developing subclinical hypothyroidism in individuals who had C alleles was 1.5 and 5.6-fold higher than in individuals without these alleles in the A2095C and A2173C regions, respectively. CONCLUSIONS: Determination of anti-TPO antibody levels and exon 12 TPO gene polymorphisms in patients with SCH can be helpful for prediction of overt hypothyroidism.

Identification of human gene research articles with wrongly identified nucleotide sequences

“…Although there have been previous reports of wrongly identified PCR primers and gene knockdown reagents in single articles or small cohorts ( 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 21 ), the present study is the first to systematically fact-check the identities of nucleotide sequences in more than 3,400 research articles. Our supported application of S&B ( 12 , 27 ) ( https://www.protocols.io/view/seek-amp-blastn-standard-operating-procedure-bjhpkj5n ) to screen three targeted corpora and two journals identified 712 articles published across 78 journals that described more than 1,500 wrongly identified sequences.…”

“…Experiments that either attempt to replicate published results associated with incorrect reagents and/or unknowingly reuse incorrect reagents are likely to generate unexpected results that may then remain unpublished. As possible evidence of this, we could only identify one study that reported incorrect sequences based on the results of follow-up experiments ( 20 ) that our analyses also identified. Given that more than 17,000 citations have been accumulated by the problematic articles that we have identified, it seems inevitable that unreliable gene research articles are already wasting time and resources.…”

“…However, as nucleotide sequences cannot be understood by eye, we have proposed that nucleotide sequence reagents are susceptible to different types of errors ( 8 , 11 , 12 ). These error types represent the equivalent of spelling errors ( 12 , 14 , 15 ), as well as identity errors, where a correct sequence is replaced by a different and possibly genetically unrelated sequence ( 11 , 12 , 13 , 16 , 17 , 18 , 19 , 20 , 21 ).…”

Molecular Mechanisms in Autoimmune Thyroid Disease

“…The TPOAb levels (and genotypes A2095C and A2173C) were significantly higher and more frequent in the subjects with SCH. The risk of developing SCH in the individuals with C alleles was higher than in the individuals without these alleles in the A2095C and A2173C regions, respectively [ 195 ].…”

Misspellings or “miscellings”-non-verifiable cell lines in cancer research publications

“…Finally, due to cross-contamination and/or uncertainty over donor origins, many human cell lines are known to be wrongly identified (21–25). These wrongly identified reagents can produce a range of downstream consequences, including failed attempts to reproduce published results (3, 5, 7, 11, 16), and potentially incorrect interpretations of preclinical data leading to misdirected translational research (10, 12, 25).…”