AUTHOR=Daher Gustavo , Santos-Bezerra Daniele Pereira , Cavaleiro Ana Mercedes , Pelaes Tatiana Souza , Admoni Sharon Nina , Perez Ricardo Vessoni , Machado Cleide Guimarães , Amaral Fernanda Gaspar do , Cipolla-Neto José , Correa-Giannella Maria Lúcia 

TITLE=Rs4862705 in the melatonin receptor 1A gene is associated with renal function decline in type 1 diabetes individuals

JOURNAL=Frontiers in Endocrinology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1331012

DOI=10.3389/fendo.2024.1331012

ISSN=1664-2392

ABSTRACT=<sec><title>Aim</title><p>The pathogenesis of chronic diabetes complications has oxidative stress as one of the major elements, and single-nucleotide polymorphisms (SNPs) in genes belonging to antioxidant pathways modulate susceptibility to these complications. Considering that melatonin is a powerful antioxidant compound, our aim was to explore, in a longitudinal cohort study of type 1 diabetes (T1D) individuals, the association of microvascular complications and SNPs in the gene encoding melatonin receptor 1A (<italic>MTNR1A</italic>).</p></sec><sec><title>Methods</title><p>Eight SNPs in <italic>MTNR1A</italic> were genotyped in 489 T1D individuals. Besides cross-sectional analyses of SNPs with each one of the microvascular complications (distal polyneuropathy, cardiovascular autonomic neuropathy, retinopathy, and diabetic kidney disease), a longitudinal analysis evaluated the associations of SNPs with renal function decline in 411 individuals followed up for a median of 8 years. In a subgroup of participants, the association of complications with urinary 6-sulfatoxymelatonin (aMT6s) concentration was investigated.</p></sec><sec><title>Results</title><p>The group of individuals with a renal function decline <underline>≥</underline> 5 mL min<sup>−1</sup> 1.73 m<sup>−2</sup> year<sup>−1</sup> presented a higher frequency of the A allele of rs4862705 in comparison with nondecliners, even after adjustment for confounding variables (OR = 1.84, 95% CI = 1.20–2.82; <italic>p</italic> = 0.0046). No other significant associations were found.</p></sec><sec><title>Conclusions</title><p>This is the first study showing an association between a variant in a gene belonging to the melatonin system and renal function decline in the diabetic setting.</p></sec>