Major intrinsic protein (MIP) polymorphism is associated with age-related cataract in Chinese

PURPOSE Age-related cataract (ARC) is a complex multi-factorial disorder involving several genetic and environmental factors. The major intrinsic protein of lens fiber gene (MIP) encodes the most abundant junctional membrane protein in the mature lens and plays a critical role in maintainace of lens normal structure and internal circulation. To determine the relationship between single nucleotide polymorphisms (SNPs) in MIP and the susceptibility to ARC in a Chinese population, we conducted this case-control study. METHODS A total of 164 unrelated ARC patients and 132 normal controls were involved in the study. All participants completed full physical and ophthalmic examinations and provided a blood sample for DNA extraction. Seven SNPs (rs2269348, rs61759527, c.-4T>C, rs77163805, rs74641138, rs35033450, and rs36032520) in MIP were amplified by polymerase chain reaction (PCR) and then sequenced. Statistical analysis was performed using SNPstats. RESULTS Polymorphisms rs61759527, rs77163805, rs35033450, and rs36032520 were not detected in all 296 subjects. There were no statistical differences in genotype or allele frequency of rs2269348 and rs74641138 between ARC cases and controls. But in c.-4C>T, cataract patients had a higher TC genotype and C allele frequencies (p=0.0018 and p=0.017, respectively) compared to healthy controls. The haplotype CCG of rs2269348, c.-4T>C and rs74641138 also exhibited a significantly higher distribution in cases than controls (OR=8.83, p=0.0024). CONCLUSIONS Our findings indicate that the genotype TC in polymorphism c.-4T>C and haplotype CCG of rs2269348, c.-4T>C, and rs74641138 in MIP may attach an additional genetic risk factor for ARC in Chinese. This is the first association study about SNPs in MIP and susceptibility to ARC in Chinese population.