Differential association of cataract sub‐types with obesity and FTO polymorphisms

Abstract Purpose Investigating a possible link between genetic variants associated with obesity and cataract may validate the causal link between obesity and cataract suggested by epidemiological studies. This study assessed the associations of obesity and genetic variants in the FTO locus, a human susceptibility locus for obesity, with cataract. Methods This was a population‐based cross‐sectional study on adults aged 40‐80 years. Cataract was assessed by standardized slit‐lamp examination according to the Lens Opacity Classification System III (LOCS III). Obesity was defined by BMI≥30kg/m2. The SNP rs9939609 at the FTO locus was selected for analysis. Additive and recessive models were constructed for the association between FTO polymorphisms and cataract. Results 3069 subjects were included, of which 1476 (48.1%) had any cataract, 927(30.2%) had nuclear cataract, 1012(33.0%) had cortical cataract and 308(10.0%) had PSC cataract. After multivariable adjustment, obesity was significantly associated with cortical (OR1.34(95% CI,1.04‐1.73)) and PSC (OR 1.53(1.07‐2.18)) cataracts, but not nuclear cataract. In the additive model, each copy of the minor allele of rs9939609 was associated with nuclear cataract (OR 1.33(1.11‐1.58)). This association persisted in multivariate analyses controlling additionally for BMI, diabetes, hypertension and smoking (OR 1.30(1.08‐1.55)). There was no association with cortical or PSC cataract. In the recessive model, rs9939609 was associated with nuclear but not cortical or PSC cataract. Conclusion Obesity is associated with cortical and PSC cataract while the SNP rs9939609 in the FTO gene is associated with nuclear cataract. The contrasting associations may reflect differences in the pathophysiology of cataract subtypes.