Evaluation of serum SLCO1B1 levels and genetic variants of SLCO1B1 rs4149056 and rs2306283 in patients with early and exudative age-related macular degeneration

Abstract

Purpose: To determine SLCO1B1 rs4149056 and rs2306283 gene polymorphisms and SLCO1B1 serum levels in patients with early and exudative age-related macular degeneration.

Materials and methods: The study enrolled 206 patients with exudative AMD, 253 patients with early AMD and 301 control subjects. DNA was extracted from peripheral venous blood leukocytes using commercial kits. Genotyping of SLCO1B1 rs4149056 and rs2306283 was carried out using a real-time polymerase chain reaction (RT-PCR) method. Serum SLCO1B1 levels were measured using SLCO1B1 ELISA kit.

Results: We found statistically significant differences in genotype (T/T, T/C and C/C) distribution of SLCO1B1 rs4149056 variant between the patients with exudative AMD and control group (52.4%, 47.6% and 0% vs. 64.8%, 31.6% and 13.7%, respectively, p < 0.001). Univariate binary logistic regression analysis showed that age was a risk factor for exudative AMD development. Also, T/C variant was associated with 1.9-fold increased Odds ratio of exudative AMD development under a codominant model (OR = 1.863; 95% CI: 1.290;2.689; p < 0.001). The results remained of the same statistical significance after multivariate analysis. On the other hand, C allele was associated with 1.6-fold increased odds ratio of exudative AMD development (OR = 1.563; 95% CI: 1.035;2.359; p = 0.034) only after adjustment for age. No significant associations were found in analysis of genotypes and alleles at rs2306283. Serum SLCO1B1 concentration was significantly higher in early AMD patients than in healthy controls (median, IQR: 2.92 ng/ml, 5.01 ng/ml versus 1.26 ng/ml, 2.63 ng/ml, respectively, p = 0.025), as well as in exudative AMD patients than in controls (median, IQR: 2.72 ng/ml, 5.71 ng/ml versus 1.26 ng/ml, 2.63 ng/ml, respectively, p = 0.002). Furthermore, subjects with rs4149056 T/C genotype had higher SLCO1B1 serum levels than those with T/T genotype (median, IQR: 3.73 ng/ml, 3.14 ng/ml versus 1.23 ng/ml, 1.47 ng/ml, respectively, p = 0.037).

Conclusion: Our study determined that SLCO1B1 (c.521 T > C) rs4149056 T/C genotype and C allele may be associated with exudative age-related macular degeneration, as well as with elevated serum SLCO1B1 levels. Also, higher serum SLCO1B1 levels were found to be associated with early and exudative age-related macular degeneration.

Keywords: Age-related macular degeneration; Gene polymorphisms; SLCO1B1; Serum SLCO1B1 levels.