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Common variation in the SERPING1 gene is not associated with age-related macular degeneration in two independent groups of subjects.

Park KH, Ryu E, Tosakulwong N, Wu Y, Edwards AO - Mol. Vis. (2009)

Bottom Line: Evaluation of haplotypes across SERPING1 did not reveal association with AMD (p=0.14-0.97).SNPs were not associated with AMD subtypes (early, geographic atrophy, or exudation).We were unable to replicate the reported association between SERPING1 and AMD in two independent groups of subjects.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Mayo Clinic, Rochester, MN 55905, USA.

ABSTRACT

Purpose: Common genetic variation in the complement component 1 inhibitor gene (SERPING1) was recently reported to increase the risk of developing age-related macular degeneration (AMD). This study was performed to replicate the association between SERPING1 and AMD.

Methods: Seven single nucleotide polymorphisms (SNPs) tagging common haplotypes across SERPING1 were genotyped on 786 (The Mayo Clinic) subjects and the association with AMD studied using single SNP and haplotype association analyses. The SNP in intron 6 (rs2511989) previously reported to increase the risk of AMD was studied in an additional 1,541 subjects from the Age-Related Eye Disease Study (AREDS). Association with specific subtypes of AMD and interaction with four other loci: complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2/LOC387715), High Temperature Requirement Factor A1 (HTRA1), complement factor B/complement component 2 (CFB/C2), and complement component 3 (C3) involved in AMD was explored.

Results: The seven tag-SNPs were not associated with AMD in the Mayo subjects (p=0.13-0.70) and rs2511989 was also not associated with AMD in the Mayo or AREDS subjects (p=0.44-0.45). Evaluation of haplotypes across SERPING1 did not reveal association with AMD (p=0.14-0.97). SNPs were not associated with AMD subtypes (early, geographic atrophy, or exudation). No interaction with other AMD risk variants was observed.

Conclusions: We were unable to replicate the reported association between SERPING1 and AMD in two independent groups of subjects.

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Related in: MedlinePlus

Linkage disequilibrium (LD) across the SERPING1 locus in HapMap (left) and Mayo subjects (right). A similar LD pattern was observed for the two independent groups of Caucasian subjects. Numbers in the squares represent r2 estimates, while colors represent D’ estimates (from none or white, to complete or red).
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f1: Linkage disequilibrium (LD) across the SERPING1 locus in HapMap (left) and Mayo subjects (right). A similar LD pattern was observed for the two independent groups of Caucasian subjects. Numbers in the squares represent r2 estimates, while colors represent D’ estimates (from none or white, to complete or red).

Mentions: To verify that our genotyping results were similar to other Caucasian populations genotyped across SERPING1, we compared the pattern of linkage disequilibrium (LD) in the Mayo subjects to the international HapMap Caucasian subjects using Haploview [48,51]. Moderate to high LD was observed across the SERPING1 locus and a similar pattern was present in the Mayo subjects and HapMap Caucasian subjects (Figure 1). The similar pattern of LD further supports the accuracy of genotyping of all seven SNPs in the Mayo subjects.


Common variation in the SERPING1 gene is not associated with age-related macular degeneration in two independent groups of subjects.

Park KH, Ryu E, Tosakulwong N, Wu Y, Edwards AO - Mol. Vis. (2009)

Linkage disequilibrium (LD) across the SERPING1 locus in HapMap (left) and Mayo subjects (right). A similar LD pattern was observed for the two independent groups of Caucasian subjects. Numbers in the squares represent r2 estimates, while colors represent D’ estimates (from none or white, to complete or red).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2629736&req=5

f1: Linkage disequilibrium (LD) across the SERPING1 locus in HapMap (left) and Mayo subjects (right). A similar LD pattern was observed for the two independent groups of Caucasian subjects. Numbers in the squares represent r2 estimates, while colors represent D’ estimates (from none or white, to complete or red).
Mentions: To verify that our genotyping results were similar to other Caucasian populations genotyped across SERPING1, we compared the pattern of linkage disequilibrium (LD) in the Mayo subjects to the international HapMap Caucasian subjects using Haploview [48,51]. Moderate to high LD was observed across the SERPING1 locus and a similar pattern was present in the Mayo subjects and HapMap Caucasian subjects (Figure 1). The similar pattern of LD further supports the accuracy of genotyping of all seven SNPs in the Mayo subjects.

Bottom Line: Evaluation of haplotypes across SERPING1 did not reveal association with AMD (p=0.14-0.97).SNPs were not associated with AMD subtypes (early, geographic atrophy, or exudation).We were unable to replicate the reported association between SERPING1 and AMD in two independent groups of subjects.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Mayo Clinic, Rochester, MN 55905, USA.

ABSTRACT

Purpose: Common genetic variation in the complement component 1 inhibitor gene (SERPING1) was recently reported to increase the risk of developing age-related macular degeneration (AMD). This study was performed to replicate the association between SERPING1 and AMD.

Methods: Seven single nucleotide polymorphisms (SNPs) tagging common haplotypes across SERPING1 were genotyped on 786 (The Mayo Clinic) subjects and the association with AMD studied using single SNP and haplotype association analyses. The SNP in intron 6 (rs2511989) previously reported to increase the risk of AMD was studied in an additional 1,541 subjects from the Age-Related Eye Disease Study (AREDS). Association with specific subtypes of AMD and interaction with four other loci: complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2/LOC387715), High Temperature Requirement Factor A1 (HTRA1), complement factor B/complement component 2 (CFB/C2), and complement component 3 (C3) involved in AMD was explored.

Results: The seven tag-SNPs were not associated with AMD in the Mayo subjects (p=0.13-0.70) and rs2511989 was also not associated with AMD in the Mayo or AREDS subjects (p=0.44-0.45). Evaluation of haplotypes across SERPING1 did not reveal association with AMD (p=0.14-0.97). SNPs were not associated with AMD subtypes (early, geographic atrophy, or exudation). No interaction with other AMD risk variants was observed.

Conclusions: We were unable to replicate the reported association between SERPING1 and AMD in two independent groups of subjects.

Show MeSH
Related in: MedlinePlus