Analysis of <i>MTNR1B</i> gene polymorphisms in relationship with <i>IRS2</i> gene variants, epicardial fat thickness, glucose homeostasis and cognitive performance in the elderly

Genome-wide association studies pinpointed common variants in or near the <i>MTNR1B</i> gene encoding MT2 melatonin receptor to be strongly associated with fasting glucose levels. <i>IRS2</i> gene polymorphisms impact insulin resistance and epicardial fat (EF) thickness, which in turn is correlated with visceral adiposity, cognitive ability and risk for metabolic plus cardiovascular disease. We aimed to discover the interactions between <i>MTNR1B</i> and <i>IRS2</i> gene polymorphisms, insulin sensitivity, EF thickness and cognitive performance in the elderly. In 60 subjects aged 60 years and older, we evaluated five single nucleotide polymorphisms (SNPs) within the <i>MTNR1B</i> locus (rs10830962, rs4753426, rs12804291, rs10830963, rs3781638), the Gly1057Asp variant of <i>IRS2</i> gene (rs1805097), biochemical parameters, cognitive performance by the Mini Mental State Examination (MMSE) and EF thickness by transthoracic echocardiography. We found that <i>MTNR1B</i> and <i>IRS2</i> gene variants impacted EF thickness, lipid profile and glucose homeostasis. <i>IRS2</i> but not <i>MTNR1B</i> variants impacted MMSE scores. In conclusion, <i>MTNR1B</i> SNPs interact with <i>IRS2</i> gene variant, correlate with the amount of epicardial adipose tissue and impact glucose homeostasis and lipid profile influencing cardiometabolic risk.