Association Between Polymorphism at IGF-1 rs35767 Gene Locus and Long-term Decline in Renal Function: A Retrospective, Cross-sectional, Longitudinal Cohort Study

<jats:title>Abstract</jats:title> <jats:p><jats:bold>Background</jats:bold>: Insulin-like growth factor-1 (IGF-1) acts on glucose and protein metabolism and human growth and also influences blood pressure and renal function. This study investigated whether the single-nucleotide polymorphism of IGF-1, rs35767, plays a role in metabolic syndrome indicators, including blood pressure, glucose metabolism, uric acid levels, and renal function.<jats:bold>Methods</jats:bold>: In this retrospective, cross-sectional, longitudinal cohort study,<jats:bold> </jats:bold>blood samples from 2601 Japanese individuals were collected and used for genotyping for variant rs35767: T > C in the IGF-1 upstream promoter. Data were analyzed to identify associations between IGF-1 genotypes and patient biochemical parameters, including the components of metabolic syndrome and the long-term change in renal function.<jats:bold>Results:</jats:bold> The cohort rs35767 genotypes included 1124 CC carriers (43.2 %), 1180 TC carriers (45.4 %), and 297 TT carriers (11.4 %). Multiple regression analysis revealed no association between IGF-1 genotype and systolic blood pressure, glycated hemoglobin level, and serum uric acid level. However, in females, diastolic blood pressure and mean blood pressure were negatively correlated with the TT genotype. In a cross-sectional analysis, factors associated with estimated glomerular filtration rate included higher mean blood pressure and glycated hemoglobin level. Longitudinal observation revealed that the decline in eGFR over 10 years was greater in TT (−18.5 ± 1.04 mL/min/1.73m<jats:sup>2</jats:sup>) than in CC carriers (−16.4 ± 0.52 mL/min/1.73m<jats:sup>2</jats:sup>; P < 0.05).<jats:bold>Conclusion: </jats:bold>The present study suggests that renal function declines faster in individuals with the<jats:bold> </jats:bold>TT genotype at the IGF-1 rs35767 locus than in those with the CC genotype, suggesting that the TT genotype is associated with the long-term chronological decline in renal function.</jats:p>