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Aryl hydrocarbon receptor gene transitions (c.-742C>T; c.1661G>A) and idiopathic male infertility: a case-control study with in silico and meta-analysis

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Abstract

Aryl hydrocarbon receptor (AHR) is responsible for crucial events in male reproductive biology. Here, the association of the AHR transitions c.-742C>T and c.1661G>A with idiopathic male infertility was investigated in a case-control study, which is followed by a meta-analysis and a bioinformatic investigation. Blood and semen samples were obtained from a total of 135 idiopathic infertile men and 130 healthy controls. Participants were genotyped for the transitions using a PCR-RFLP method. A meta-analysis of five sets of data evaluated the association of c.1661G>A with male infertility, and using an in silico analysis, the possible molecular effects of the transitions predicted. Genotypes and alleles of AHR-c.-742C>T and c.1661G>A polymorphisms were not associated with the risk of male infertility significantly. However, the frequency of C/A haplotype was significantly associated with the increased risk of male infertility, and T/A haplotype was higher among controls significantly. Also, the frequencies of combined genotypes CT/GG, CT/GA and TT/GG were significantly associated with decreased risk of infertility. And, the meta-analysis showed that the AA versus GA/GG recessive model is associated with decreased risk of male infertility among the Iranian population. In silico analysis predicted that c.-742C>T does not alter the binding sites of the proposed transcription factors, but c.1661G>A poses a tolerable structural disturbance in AHR protein. In conclusion, these results showed that AHR c.-742C>T and c.1661G>A transitions separately could not be nominated as a risk or protective factor for male infertility. However, some combined models could affect infertility risk, especially among Iranian men.

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Acknowledgements

We gratefully acknowledge Prof. Andres Salumets from the University of Tartu for providing us with his case-control study data, as well as Mr. Esmaiel Nouri for his help in the grammatical editing of the manuscript.

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Correspondence to Abasalt Hosseinzadeh Colagar.

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This study was approved by the Ethics Committees of Mazandaran University of Medical Science (#MUBABOL.REC.1395.189) and informed consent was obtained from subjects.

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This work was supported by a grant from the University of Mazandaran, dedicated to the PhD thesis of Younes Aftabi.

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Aftabi, Y., Hosseinzadeh Colagar, A., Mehrnejad, F. et al. Aryl hydrocarbon receptor gene transitions (c.-742C>T; c.1661G>A) and idiopathic male infertility: a case-control study with in silico and meta-analysis. Environ Sci Pollut Res 24, 20599–20615 (2017). https://doi.org/10.1007/s11356-017-9701-2

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