Variation in optineurin (OPTN) allele frequencies betweenand within populations

[摘要] Purpose: To evaluate the extent to which mutations in theoptineurin (OPTN) glaucoma gene play a role in glaucoma indifferent populations.Methods: Case-controlled study of OPTN sequence variants inindividuals with or without glaucoma in populations of differentancestral origins and evaluate previous OPTN reports. We analyzed314 subjects with African, Asian, Caucasian and Hispanic ancestriesincluded 229 cases of primary open-angle glaucoma, 51 cases ofjuvenile-onset open-angle glaucoma, 33 cases of normal tension glaucoma,and 371 controls. Polymerase chain reaction-amplified OPTN codingexons were resequenced and case frequencies were compared to frequenciesin controls matched for ancestry.Results: The E50K sequence variant was identified in one individualfrom Chile with normal tension glaucoma, and the 691_692insAG variantwas found in one Ashkenazi Jewish individual from Russia. The R545Qvariant was found in two Asian individuals with primary open-angleglaucoma; one of Filipino ancestry and one of Korean ancestry. Inaddition to presenting OPTN allele frequencies for Caucasian andAsian populations that have been the subject of previous reports, wealso present information for populations of Hispanic and black Africanancestries.Conclusions: Our study contributes additional evidence to supportthe previously reported association of the OPTN E50K mutation withglaucoma. After finding an additional 691_692insAG OPTN variant, wecan still only conclude that this variant is rare. Combined analysis ofour data with data from more than a dozen other studies indicates noassociation of R545Q with glaucoma in most populations. Those samestudies disagree in their conclusions regarding the role of M98K inglaucoma. Our analysis of the combined data provides statisticallysignificant evidence of association of M98K with normal tension glaucomain Asian populations, but not in Caucasian populations; however, thevalidity of this conclusion is questionable because of large differencesin allele frequencies between and within populations. It is currentlynot possible to tell how much of the underlying cause of the allelefrequency difference is attributable to demographic, technical, orascertainment differences among the studies.

[学科分类] 生物化学/生物物理