Association of LDLR rs688 Polymorphism With Dyslipidemia in End-Stage Renal Disease: A Case-Control Study

Background End-stage renal disease (ESRD) is associated with substantial cardiovascular morbidity, partly because advanced renal failure is accompanied by metabolic and lipid disturbances. The LDLR gene plays a key role in cholesterol homeostasis, and rs688 may influence low-density lipoprotein (LDL) receptor function and lipid handling. This exploratory case-control study evaluated the association of LDLR rs688 polymorphism with ESRD status and serum lipid abnormalities; it was not designed to determine incident cardiovascular events or specific cardiovascular disease (CVD) subtypes. Methodology The study involved 100 participants, including 50 clinically diagnosed patients with ESRD and 50 apparently healthy controls with no known kidney disease or clinically evident systemic disease at recruitment. Biochemical, genotype, and structured reference data were combined using participant identifiers to create a harmonized analytic dataset. Serum creatinine, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were analyzed. Genotype analysis for LDLR rs688 classified participants as CC, CT, or TT. Genotype and allele frequencies were tested by chi-square analysis, Hardy-Weinberg equilibrium was assessed in controls, genotype-lipid associations were assessed by one-way analysis of variance, and logistic regression estimated the association between rs688 and ESRD status with adjustment for age and sex. Results Individuals with ESRD were significantly older than controls and had markedly higher levels of serum creatinine, total cholesterol, triglycerides, and LDL-C. HDL-C levels were significantly lower. The distribution of genotypes of LDLR rs688 was significantly different between patients with ESRD and controls. Patients with ESRD showed a higher frequency of the TT genotype (n = 14, 28.0%) than controls (n = 2, 4.0%) (p = 0.001). In the entire group, HDL-C (p = 0.015) and LDL-C (p = 0.045) varied by genotype, with the TT carriers having the most unfavorable LDL-C profile. Logistic regression showed that rs688 was associated with higher odds of ESRD status, not incident CVD risk. The strongest association was observed under the recessive model (odds ratio (OR) = 9.33, 95% confidence interval (CI) = 1.99-43.68, p = 0.005), which remained significant after adjustment for age and sex (adjusted OR = 7.12, 95% CI = 1.22-41.60, p = 0.029). Conclusions The TT genotype of LDLR rs688 was associated with an unfavorable lipid profile in the overall cohort and higher odds of ESRD status. These findings suggest that LDLR-related genetic variation may contribute to metabolic derangement and ESRD susceptibility. Because this was a small exploratory case-control study with limited comorbidity and medication data, the results should be interpreted as preliminary and require confirmation in larger, ethnically diverse cohorts with more complete clinical adjustment.