Associations between ZNF676, CTC 1 Gene Polymorphisms and Relative Leukocyte Telomere Length with Myopia and Its Degree

Abstract

Background: The interaction between environmental and genetic factors that influence eye growth, regulated by vision, contributes to the development and progression of myopia. This dynamic interaction significantly contributes to the multifaceted development and progression of myopia, a prevalent ocular condition. Our study delves into the associations between ZNF676 and CTC1 gene polymorphisms and their impact on the relative leukocyte telomere length (relative LTL) in myopia, as well as its degree. By unravelling these underpinnings in conjunction with environmental influences, we aim to enhance our understanding of the complex mechanisms that drive the onset and severity of myopia.

Methods: This study included patients with myopia and ophthalmologically healthy subjects. DNA was extracted from peripheral venous blood by the salting out method. Genotyping of ZNF676 rs412658 and CTC1 rs3027234, as well as the measurement of relative LTL, were conducted using a real-time polymerase chain reaction method (RT-PCR). The data obtained were statistically analyzed using the "IBM SPSS Statistics 29.0" software program.

Results: The results show that myopic patients who are homozygous for the rs3027234 rare allele genotype of the CTC1 gene have statistically significantly shorter relative LTL compared to patients with the CC and CT genotypes. Also, men with the CTC1 rs3027234 TT genotype have statistically significantly longer leukocyte telomeres than women with the same genotype. The respective median (IQR) of the relative LTL for women and men is 0.280 (0.463) vs. 0.696 (0.440), with a p-value of 0.027. The myopia group with the ZNF676 rs412658 CC genotype has statistically significantly shorter leukocyte telomeres than the control group with the same genotype (age ≤ 29), and the p-value is 0.011. Also, the myopia group with the ZNF676 rs412658 CT and CTC1 rs3027234 CT genotypes have statistically significantly longer leukocyte telomeres than the control group with the same genotypes (age > 29), with p-values that are, respectively, 0.016 and 0.012. The evaluation of the genotype distributions of the polymorphisms in the myopia patients showed that ZNF676 rs412658 CT genotype carriers have 4-fold decreased odds of high myopia occurrence (OR = 0.250; CI: 0.076-0.826; p = 0.023). Also, the evaluation of the allele distributions of the polymorphism under the additive genetic model in the myopia group showed that the ZNF676 rs412658 T allele was associated with similar odds of high myopia (OR = 0.269; 95% CI: 0.090-0.807; p = 0.019). The comprehensive p-value, assessing the relative LTL of subjects across the different levels of myopia, signifies a statistical difference in the relative LTL among individuals with varying degrees of myopia. There was a statistically significant difference in relative LTL between mild and moderate myopia degrees (0.819 (1.983) vs. 0.083 (0.930), p = 0.007).

Conclusions: CTC1 rs3027234 TT may be considered a protective genotype for telomere shortening in men, while the overall telomere shortening might be linked to the worse myopia degree. The ZNF676 rs412658 T allele may protect against a high myopia occurrence.

Keywords: CTC1; ZNF676; myopia; relative leukocyte telomere length; rs3027234; rs412658.

Figure 1

Relative leukocyte telomere length in control and myopia groups. The X-axis shows the study groups, the Y-axis shows the relative leukocyte telomere length, and the blue rectangles divided by the medians denote the quartiles. The lower part is the first quartile, and the upper part is the third quartile; p-value is the significance level (differences are considered statistically significant if p < 0.05).

Figure 2

Relative leukocyte telomere length’s association with ZNF676 rs412658 and CTC1 rs3027234 gene polymorphisms in subjects. Blue rectangles, divided by medians, denote quartiles. The lower part is the first quartile, and the upper part is the third quartile. The X-axis represents polymorphism genotypes, the Y-axis indicates relative leukocyte telomere length; p-value indicates the level of significance (differences are considered statistically significant when p < 0.05). (A)—the relationship between relative leukocyte telomere length and ZNF676 rs412658 polymorphism in both groups; (B)—the relationship between relative leukocyte telomere length and CTC1 rs3027234 polymorphism in both groups; (C)—the relationship between relative leukocyte telomeres and ZNF676 rs412658 polymorphism in the myopia group; (D)—the relationship between relative leukocyte telomeres and CTC1 rs3027234 polymorphism in the myopia group; (E)—the relationship between relative leukocyte telomeres and ZNF676 rs412658 polymorphism in the control group; (F)—the relationship between relative leukocyte telomeres and CTC1 rs3027234 polymorphism in the control group.

Figure 3

Comparison of relative leukocyte telomere length and genotypes of ZNF676 rs412658 and CTC1 rs3027234 gene polymorphisms in male and female groups in all study participants. (A,B) On the X-axis, the genotypes of ZNF676 rs412658 and CTC1 rs3027234 gene polymorphisms are illustrated, with the Y-axis representing the relative leukocyte telomere length. Red and green rectangles, separated by medians, signify quartiles. The lower segment represents the first quartile, and the upper segment represents the third quartile. The p-value indicates the level of significance, with differences considered statistically significant when p < 0.05.

Figure 4

Comparison of relative leukocyte telomere length and genotypes of ZNF676 rs412658 and CTC1 rs3027234 gene polymorphisms in two age groups. (A,B) Groups’ age is less or equal to 29 years old; (C,D) groups are more than 29 years old. On the X-axis, the genotypes of ZNF676 rs412658 and CTC1 rs3027234 gene polymorphisms are illustrated, with the Y-axis representing the relative leukocyte telomere length. Red and green rectangles, separated by medians, signify quartiles. The lower segment represents the first quartile, and the upper segment represents the third quartile. The p-value indicates the level of significance, with differences considered statistically significant when p < 0.05. *—Mann–Whitney U test was used; **—Student‘s t-Test was used.

Figure 5

Myopia degree associations with relative leukocyte telomere length. The weak, moderate, and high myopia degrees are illustrated on the X-axis, with the Y-axis representing the relative leukocyte telomere length. Blue, pink, and purple rectangles, separated by medians, signify quartiles. The lower segment represents the first quartile, and the upper segment represents the third quartile. The p-value indicates the level of significance, with differences considered statistically significant when p < 0.05.