The impact of homocysteine on patients with diabetic nephropathy: a mendelian randomization study.

ABSTRACT

BACKGROUND/AIMS: Homocysteine (Hcy) has been associated with an increased risk of diabetic nephropathy (DN) in patients, but there is still controversy. This study aims to investigate the causal relationship between plasma Hcy and DN. METHODS: A Mendelian randomization (MR) study using data from 2 samples was employed to infer causal relationships. The aggregated genetic data associated with Hcy was derived from the largest genome-wide association study (GWAS) to date, involving 44,147 individuals of European ancestry.Data on SNP-diabetic nephropathy, creatinine, and urea nitrogen were obtained from the IEU GWAS database. The analysis method employed a fixed-effect or random-effect inverse variance-weighted approach to estimate effects.Additional analysis methods were used to assess stability and sensitivity. The potential for pleiotropy was evaluated using the MR-Egger intercept test. RESULTS: Using 12 SNPs as instrumental variables, two-sample MR analysis revealed no evidence of a causal relationship between genetically predicted plasma Hcy levels and diabetic nephropathy, as well as creatinine and blood urea nitrogen levels. This finding is consistent with the results obtained from other testing methods. CONCLUSIONS: Two-sample Mendelian Randomization analysis found no evidence of a causal relationship between plasma homocysteine levels and diabetic nephropathy, creatinine, or urea.