5 research outputs found
Variation in optineurin (OPTN) allele frequencies between and within populations
PURPOSE: To evaluate the extent to which mutations in the optineurin (OPTN) glaucoma gene play a role in glaucoma in
different populations.
METHODS: Case-controlled study of OPTN sequence variants in individuals with or without glaucoma in populations of
different ancestral origins and evaluate previous OPTN reports. We analyzed 314 subjects with African, Asian, Caucasian
and Hispanic ancestries included 229 cases of primary open-angle glaucoma, 51 cases of juvenile-onset open-angle glaucoma,
33 cases of normal tension glaucoma, and 371 controls. Polymerase chain reaction-amplified OPTN coding exons
were resequenced and case frequencies were compared to frequencies in controls matched for ancestry.
RESULTS: The E50K sequence variant was identified in one individual from Chile with normal tension glaucoma, and the
691_692insAG variant was found in one Ashkenazi Jewish individual from Russia. The R545Q variant was found in two
Asian individuals with primary open-angle glaucoma; one of Filipino ancestry and one of Korean ancestry. In addition to
presenting OPTN allele frequencies for Caucasian and Asian populations that have been the subject of previous reports,
we also present information for populations of Hispanic and black African ancestries.
CONCLUSIONS: Our study contributes additional evidence to support the previously reported association of the OPTN E50K
mutation with glaucoma. After finding an additional 691_692insAG OPTN variant, we can still only conclude that this
variant is rare. Combined analysis of our data with data from more than a dozen other studies indicates no association of
R545Q with glaucoma in most populations. Those same studies disagree in their conclusions regarding the role of M98K
in glaucoma. Our analysis of the combined data provides statistically significant evidence of association of M98K with
normal tension glaucoma in Asian populations, but not in Caucasian populations; however, the validity of this conclusion
is questionable because of large differences in allele frequencies between and within populations. It is currently not
possible to tell how much of the underlying cause of the allele frequency difference is attributable to demographic, technical, or ascertainment differences among the studies
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Amerindian ancestry proportion as a risk factor for inflammatory bowel diseases: results from a Latin American Andean cohort.
BACKGROUND AND AIMS: Latin American populations remain underrepresented in genetic studies of inflammatory bowel diseases (IBDs). Most genetic association studies of IBD rely on Caucasian, African, and Asian individuals. These associations have yet to be evaluated in detail in the Andean region of South America. We explored the contribution of IBD-reported genetic risk variants to a Chilean cohort and the ancestry contribution to IBD in this cohort. METHODS: A total of 192 Chilean IBD patients were genotyped using Illuminas Global Screening Array. Genotype data were combined with similar information from 3,147 Chilean controls. The proportions of Aymara, African, European, and Mapuche ancestries were estimated using the software ADMIXTURE. We calculated the odds ratios (ORs) and 95% confidence intervals (CIs) for gender, age, and ancestry proportions. We also explored associations with previously reported IBD-risk variants independently and in conjunction with genetic ancestry. RESULTS: The first and third quartiles of the proportion of Mapuche ancestry in IBD patients were 24.7 and 34.2%, respectively, and the corresponding OR was 2.30 (95%CI 1.52-3.48) for the lowest vs. the highest group. Only one variant (rs7210086) of the 180 reported IBD-risk SNPs was associated with IBD risk in the Chilean cohort (adjusted P = 0.01). This variant is related to myeloid cells. CONCLUSION: The type and proportion of Native American ancestry in Chileans seem to be associated with IBD risk. Variants associated with IBD risk in this Andean region were related to myeloid cells and the innate immune response
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Amerindian ancestry proportion as a risk factor for inflammatory bowel diseases: results from a Latin American Andean cohort
Peer reviewed: TrueAcknowledgements: The authors are indebted to Dr. Justo Lorenzo-Bermejo and collaborators from his group, Dr. Linda Zollner, Dr. Carol Barahona Ponce, Dr. Felix Boekstegers, and EULAT Eradicate GBC, for sharing the genotypic and sociodemographic information from control individuals as well as providing expert advice on statistical analysis. This study and its research would not have been possible without the exceptional support of the patients, nurses, technicians, and medical scheduler from the Endoscopy Unit of the Hospital San Borja Arriarán, Santiago, Chile.Background and aimsLatin American populations remain underrepresented in genetic studies of inflammatory bowel diseases (IBDs). Most genetic association studies of IBD rely on Caucasian, African, and Asian individuals. These associations have yet to be evaluated in detail in the Andean region of South America. We explored the contribution of IBD-reported genetic risk variants to a Chilean cohort and the ancestry contribution to IBD in this cohort.MethodsA total of 192 Chilean IBD patients were genotyped using Illumina's Global Screening Array. Genotype data were combined with similar information from 3,147 Chilean controls. The proportions of Aymara, African, European, and Mapuche ancestries were estimated using the software ADMIXTURE. We calculated the odds ratios (ORs) and 95% confidence intervals (CIs) for gender, age, and ancestry proportions. We also explored associations with previously reported IBD-risk variants independently and in conjunction with genetic ancestry.ResultsThe first and third quartiles of the proportion of Mapuche ancestry in IBD patients were 24.7 and 34.2%, respectively, and the corresponding OR was 2.30 (95%CI 1.52–3.48) for the lowest vs. the highest group. Only one variant (rs7210086) of the 180 reported IBD-risk SNPs was associated with IBD risk in the Chilean cohort (adjusted P = 0.01). This variant is related to myeloid cells.ConclusionThe type and proportion of Native American ancestry in Chileans seem to be associated with IBD risk. Variants associated with IBD risk in this Andean region were related to myeloid cells and the innate immune response.</jats:sec