Ayala-Haedo Juan A, Gallins Paul J, Whitehead Patrice L, Schwartz Stephen G, Kovach Jaclyn L, Postel Eric A, Agarwal Anita, Wang Gaofeng, Haines Jonathan L, Pericak-Vance Margaret A, Scott William K
John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Ann Hum Genet. 2010 May;74(3):195-201. doi: 10.1111/j.1469-1809.2010.00570.x. Epub 2010 Mar 31.
Age-related macular degeneration (AMD) is a complex degenerative retinal disease influenced by both genetic and environmental risk factors. We assessed whether single nucleotide polymorphisms (SNPs) in the NOS2A gene increase risk and modulate the effect of smoking in AMD. 998 Caucasian subjects (712 AMD cases and 286 controls) were genotyped for 17 SNPs in NOS2A. Multivariable logistic regression models containing SNP genotypes, age, sex, smoking status and genotype/smoking interaction were constructed. SNP rs8072199 was significantly associated with AMD (OR = 1.3; 95% CI : 1.02, 1.65; P = 0.035). A significant interaction with smoking was detected at rs2248814 (P = 0.037). Stratified data by genotypes demonstrated that the association between AMD and smoking was stronger in carriers of AA genotypes (OR = 35.98; 95% CI: 3.19, 405.98) than in carriers of the AG genotype (OR = 3.05; 95% CI: 1.36, 6.74) or GG genotype (OR = 2.1; 95% CI: 0.91, 4.84). The results suggest a possible synergistic interaction of AA genotype with smoking, although the result bears replication in larger samples. Our data suggests that SNPs in the NOS2A gene are associated with increased risk for AMD and might modulate the effect of smoking on AMD.
年龄相关性黄斑变性（AMD）是一种复杂的视网膜退行性疾病，受遗传和环境风险因素的影响。我们评估了NOS2A基因中的单核苷酸多态性（SNP）是否会增加AMD的风险并调节吸烟对其的影响。对998名白种人受试者（712例AMD患者和286名对照）进行了NOS2A基因中17个SNP的基因分型。构建了包含SNP基因型、年龄、性别、吸烟状况和基因型/吸烟相互作用的多变量逻辑回归模型。SNP rs8072199与AMD显著相关（OR = 1.3；95% CI：1.02，1.65；P = 0.035）。在rs2248814处检测到与吸烟有显著的相互作用（P = 0.037）。按基因型分层的数据表明，AA基因型携带者中AMD与吸烟之间的关联比AG基因型携带者（OR = 3.05；95% CI：1.36，6.74）或GG基因型携带者（OR = 2.1；95% CI：0.91，4.84）更强。结果表明AA基因型与吸烟之间可能存在协同相互作用，尽管该结果需要在更大样本中进行重复验证。我们的数据表明，NOS2A基因中的SNP与AMD风险增加相关，并且可能调节吸烟对AMD的影响。
