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Interleukin Gene Polymorphisms in Age-Related Macular Degeneration

¹From the Departments of Ophthalmology, ²Medical Genetics, and ³Medical Research, China Medical University Hospital, Taichung, Taiwan; the ⁴Department of Biotechnology and Bioinformatics, Asia University, Taichung, Taiwan; the ⁵Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan; and the ⁶Department of Ophthalmology, National Cheng Kung University Hospital, Tainan, Taiwan.

PURPOSE. To investigate polymorphisms in a candidate gene of interleukin (IL) in unrelated Taiwan Chinese patients with late age-related macular degeneration (AMD) and control subjects without AMD.

METHODS. In this retrospective, case-control study, 312 unrelated Taiwan Chinese patients with late AMD and 180 age- and sex-matched control subjects were enrolled. Late AMD was classified as either atrophic (dry) or neovascular (wet) according to the International ARM Epidemiologic Study. Genomic DNA was prepared from peripheral blood obtained from all patients with AMD and control subjects. Polymerase chain reactions were used to analyze 14 single-nucleotide polymorphisms (SNPs) in candidate genes of 5 ILs: IL-1β(2q14): –511 T/C; IL-6 (7p21): –572 C/G and –596 G/A; IL-8 (4q13-q21): –251 A/T, +781 C/T, +1633 T/C, and +2767 A/T; IL-10 (1q31-q32): –592 A/C, –819 C/T, and –1082 G/A; and IL-18 (11q22.2-q22.3): +105 A/C, –137 C/G, –607 A/C, and –656 T/G.

RESULTS. In the 312 patients with late AMD, dry AMD was diagnosed in 136 and wet AMD in 176. Among the 14 SNPs in the 5 IL genes studied, only the IL-8 +781 C/T SNP was significantly associated with wet AMD (T allele: 46% in wet AMD versus 28% in the control subjects, P = 1.03 x 10^–6, OR = 2.16, 95% CI = 1.58–2.94). The association analysis based on genotypes at both IL-8 +781 C/T and the CFH Y402H demonstrated that the IL-8 +781 C/T to AMD was not significant when analyzed conditional on the presence of the CFH Y402H C risk allele and vice versa. The IL-8 +781 C/T was in low linkage disequilibrium with CFH Y402H (D' = 0.02).

CONCLUSIONS. The data suggest that Taiwan Chinese carriers of the IL-8 +781 T allele, independent of the CFH Y402H polymorphism, are at increased risk of developing wet AMD.