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

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.