Associations of Polymorphisms in MTHFR Gene with the Risk of Age-Related Cataract in Chinese Han Population: A Genotype-Phenotype Analysis

Abstract

Homocysteine (Hcy) is a potential risk factor for age-related cataract (ARC). Methylenetetrahydrofolate reductase (MTHFR) is the key enzyme for Hcy metabolism, and variants of MTHFR may affect MTHFR enzyme activity. This study mainly evaluated the associations between variants in MTHFR gene, plasma MTHFR enzyme activity, total Hcy (tHcy) levels and ARC risk in Chinese population. Four single nucleotide polymorphisms (SNPs) in MTHFR gene were genotyped using the high-resolution melting (HRM) method in 502 ARC patients (mean age, 70.2 [SD, 9.0], 46.0% male) and 890 healthy controls (mean age, 67.1 [SD, 11.1], 47.6% male). The plasma MTHFR activity, folic acid (FA), vitamins B12 and B6 levels were detected by enzyme-linked immunosorbent assays (ELISA). The plasma tHcy levels were measured by an automated enzymatic assay. After the Bonferroni correction, the minor allele T of SNP rs1801133 showed a significant association with an increased risk of overall ARC (OR = 1.26, P = 0.003). Consistent association was also found between SNP rs1801133 and cortical ARC risk (OR = 1.44, P = 0.003). Haplotype analyses revealed an adverse effect of the haplotype "C-A-T-C" (alleles in order of SNPs rs3737967, rs1801131, rs1801133 and rs9651118) on ARC risk (OR = 1.55, P = 0.003). Moreover, in a joint analysis of SNPs rs9651118 and rs1801133, subjects with two unfavorable genotypes had a 1.76-fold increased risk of ARC compared with the reference group, and a statistically significant dose-response trend (Ptrend = 0.001) was also observed. Further, in healthy controls and patients with cortical ARC, the allele T of SNP rs1801133 and the increasing number of unfavorable genotypes were significantly correlated with decreased MTHFR activity as well as increased tHcy levels. However, there was no significant association between FA, vitamins B12, B6 levels and MTHFR variants. Our data indicated that variants in MTHFR gene might individually and jointly influence susceptibility to ARC by affecting MTHFR enzyme activity and tHcy levels.

HDAC9 Variant Rs2107595 Modifies Susceptibility to Coronary Artery Disease and the Severity of Coronary Atherosclerosis in a Chinese Han Population

“…Genomic DNA of peripheral blood leukocytes was isolated by a phenol/chloroform method. SNP rs2107595 was genotyped by high resolution melting (HRM) analyses using a LightScanner 96 system (Idaho Technology, Salt Lake City, UT, USA)[ 20 , 21 ], as described in S1 Table . Repeated assays and DNA sequence analysis were used to validate the accuracy of HRM genotyping ( S1 Fig ).…”

Associations of polymorphisms in TXNIP and gene–environment interactions with the risk of coronary artery disease in a Chinese Han population

“…Genomic DNA was prepared from peripheral blood leucocytes using a phenol/chloroform method. SNP genotyping was conducted with high resolution melting (HRM) analyses on a LightScanner 96 system (Idaho Technology, Salt Lake City, UT, USA), as described previously . The accuracy of genotyping was confirmed by repeated assays (Fig.…”

Polygenetic-Risk Scores Related to Crystallin Metabolism Are Associated with Age-Related Cataract Formation and Interact with Hyperglycemia, Hypertension, Western-Style Diet, and Na Intake

“…Furthermore, the rs1801133 polymorphism of methylenetetrahydrofolate reductase ( MTHFR ) exhibits a significant association with ARC. The minor MTHFR T allele of rs1801133 has a positive association with ARC risk (OR = 1.26, p = 0.003) and the s3737967, rs1801131, rs1801133 haplotypes (OR = 1.55, p = 0.003) and MTHFR rs9651118 are also linked to ARC risk [ 9 ]. Interestingly, MTHFR is involved in homocysteine metabolism and also modulates serum concentrations of homocysteine—a potential risk factor for insulin resistance.…”

“…Interestingly, MTHFR is involved in homocysteine metabolism and also modulates serum concentrations of homocysteine—a potential risk factor for insulin resistance. The minor allele rs1801133 of MTHFR decreases its activity and may increase serum homocysteine concentrations, which would increase the risk of both ARC and metabolic syndrome [ 9 ]. These results suggest that genetic risk factors for metabolic syndrome, as well as dietary and environmental factors that exacerbate the genetic risk factors, may be important risk factors for ARC.…”