Researchers uncover gene variation linked to AMD

A case-control study has uncovered a specific variation in the SERPING1 gene that can significantly influence vulnerability to age-related macular degeneration.

"SERPING1 encodes the C1 inhibitor, which has a crucial role in inhibition of complement component 1 (C1) and might implicate the classic pathway of complement activation in this disease," the study authors said in The Lancet.

To identify possible genetic risk factors for the disease, Sarah Ennis, PhD, and colleagues used 93 single nucleotide polymorphisms to perform low-density screen tests of the SERPING1 gene, as well as 31 additional candidate genes, in a cohort comprised 479 patients with AMD and 479 unaffected controls in the United Kingdom.

Subsequently, the investigators confirmed all significant initial findings by replicating the trial in an independent cohort of 248 unrelated AMD patients and 252 non-AMD controls in the United States.

High-density genotyping around association signals was performed for both populations.

The researchers found that a single nucleotide polymorphism (SNP) variant located within intron six of the SERPING1 gene, called rs2511989, demonstrated a statistically significant genetic link with AMD (P = .00372); however, none of the 31 additional gene candidates were associated with the disease.

Compared with wild type G/G homozygotes, the odds ratio for AMD in rs2511989 G/A heterozygotes was 0.63; the odds ratio for AMD was 0.44 when comparing A/A homozygotes with the wild type, the authors noted.

These genotypic associations were similar in the U.S. cohort (P = .008).

In a secondary high-density genotype study of the SERPING1 gene region, the researchers identified five additional SNP gene variants that were associated with AMD, according to the study.