Mercury exposure, epigenetic modifications, and genetic susceptibility: insights from molecular docking and population analysis

Bakhtiyar Serik¹Lyazzat E. Shinetova²Natalya V. Efimova³Saulemay A. Bekeeva⁴Balkiya M. Abdrakhmanova⁵Aliya O. Dauletova⁴Roza K. Suleimenova⁴Nadiar Maratovich Mussin⁶Afshin Zare⁷Ramazon Safarzoda Sharoffidin⁸Amin Tamadon^9*

• ¹Manash Kozybayev North Kazakhstan University, Petropavl, Kazakhstan
• ²National Testing Center, Astana, Kazakhstan, Astana, Kazakhstan
• ³East Siberian Institute of Medical and Ecological Research, Angarsk, Russia
• ⁴S Seifullin Kazakh Agro Technical Research University, Astana, Kazakhstan
• ⁵L N Gumilyov Eurasian National University, Astana, Kazakhstan
• ⁶West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
• ⁷Taipei Medical University, Taipei City, Taiwan
• ⁸Avicenna Tajik State Medical University, Dushanbe, Tajikistan
• ⁹West Kazakhstan Marat Ospanov State Medical University, Aktobe, Fars province, Kazakhstan

Mercury (Hg) is a major environmental contaminant and a pressing public health concern, especially in industrial regions where metallurgical activities release Hg into the environment. This study assessed genetic susceptibility to mercury toxicity among 180 residents of Temirtau (Kazakhstan) and 90 controls by analyzing GSTM1, GSTT1, GSTP1 (Ile105Val, rs1695), and GCLM (–588C/T, rs41303970) polymorphisms. Mercury concentrations were quantified in blood and hair samples using cold-vapor atomic absorption spectrometry, and dietary information was collected to identify major exposure routes. Genotyping was performed by PCR and PCR-RFLP methods. In a complementary molecular-docking analysis, methylmercury (MeHg) interactions with key epigenetic regulators—DNA methyltransferase 1 (DNMT1), histone deacetylases (HDAC1-6), and sirtuin 1 (SIRT1)—were modeled. Docking revealed moderate affinity of MeHg within catalytic domains of DNMT1 and HDAC isoforms, suggesting potential interference with DNA methylation and histone-modification processes. Individuals carrying GSTM1-null and GCLM variant genotypes exhibited higher Hg accumulation and oxidative-stress susceptibility. Although exposure levels were much lower than those observed in classical Minamata incidents, measurable subclinical effects and genotype–environment associations were evident. These findings highlight an oxidative-stress–driven, epigenetic-dysregulation mechanism underlying inter-individual variability in mercury toxicity and underscore the value of integrating genetic and molecular-modeling approaches for risk assessment in industrially exposed populations.