Analysis of copy number variation at DMBT1 and age-related macular degeneration

作者：Polley, Shamik; Cipriani, Valentina; Khan, Jane C.; Shahid, Humma; Moore, Anthony T.; Yates, John R. W.; Hollox, Edward J.^*

来源：BMC Medical Genetics, 2016, 17(1): 44.

DOI：10.1186/s12881-016-0311-5

• COMPLEMENT FACTOR-H
• STRONG ASSOCIATION
• BACTERIA BINDING
• LECTIN PATHWAY
• RISK-FACTORS
• SUSCEPTIBILITY
• VARIANT
• DISEASE
• CFH
• POLYMORPHISMS

Background: DMBT1 is a gene that shows extensive copy number variation (CNV) that alters the number of bacteria-binding domains in the protein and has been shown to activate the complement pathway. It lies next to the ARMS2/HTRA1 genes in a region of chromosome 10q26, where single nucleotide variants have been strongly associated with age-related macular degeneration (AMD), the commonest cause of blindness in Western populations. Complement activation is thought to be a key factor in the pathogenesis of this condition. We sought to investigate whether DMBT1 CNV plays any role in the susceptibility to AMD.
Methods: We analysed long-range linkage disequilibrium of DMBT1 CNV1 and CNV2 with flanking single nucleotide polymorphisms (SNPs) using our previously published CNV and HapMap Phase 3 SNP data in the CEPH Europeans from Utah (CEU). We then typed a large cohort of 860 AMD patients and 419 examined age-matched controls for copy number at DMBT1 CNV1 and CNV2 and combined these data with copy numbers from a further 480 unexamined controls.
Results: We found weak linkage disequilibrium between DMBT1 CNV1 and CNV2 with the SNPs rs1474526 and rs714816 in the HTRA1/ARMS2 region. By directly analysing copy number variation, we found no evidence of association of CNV1 or CNV2 with AMD.
Conclusions: We have shown that copy number variation at DMBT1 does not affect risk of developing age-related macular degeneration and can therefore be ruled out from future studies investigating the association of structural variation at 10q26 with AMD.

• 出版日期2016-7-15