HTRA1 rs11200638 variant and AMD risk from a comprehensive analysis about 15,316 subjects

The high-temperature requirement factor A1 (HTRA1) gene located at 10q26 locus has been associated with age-related macular degenerative (AMD), with the significantly related polymorphism being (rs11200638, -625G/A), however, above association is not consistent. We investigated a comprehensive analysis to evaluate the correlations between rs11200638 polymorphism and AMD susceptibility thoroughly addressing this issue.

An identification was covered from the PubMed and Wanfang databases until 27th Jan, 2020. Odds ratios (OR) with 95% confidence intervals (CI) were applied to evaluate the associations. After a thorough and meticulous search, 35 different articles (33 case-control studies with HWE, 22 case-control studies about wet/dry AMD) were retrieved.

Individuals carrying A-allele or AA genotype may have an increased risk to be AMD disease. For example, there has a significantly increased relationship between rs11200638 polymorphism and AMD both for Asians (OR: 2.51, 95%CI: 2.22-2.83 for allelic contrast) and Caucasians [OR (95%CI) = 2.63(2.29-3.02) for allelic contrast]. Moreover, a similar trend in the source of control was detected. To classify the type of AMD, increased association was also observed in both wet (OR: 3.40, 95%CI: 2.90-3.99 for dominant model) and dry (OR: 2.08, 95%CI: 1.24-3.48 for dominant model) AMD. Finally, based on the different genotyping methods, increased relationships were identified by sequencing, TaqMan, PCR-RFLP and RT-PCR.

Our meta-analysis demonstrated that HTRA1 rs11200638 polymorphism may be related to the AMD development, especially about individuals carrying A-allele or AA genotype, who may be as identified targets to detect and intervene in advance. Further studies using Larger sample size studies, including information about gene-environment interactions will be necessary to carry out.