Association of TNF-α gene alterations (c.-238G>A, c.-308G>A, c.-857C>T, c.-863C>A) with primary glaucoma in north Indian cohort.
Gene
; 709: 25-35, 2019 Aug 15.
Article
en En
| MEDLINE
| ID: mdl-31132515
ABSTRACT
BACKGROUND:
Tumor Necrosis Factor-alpha (TNF-α) a pleuripotent pro-inflammatory cytokine, is involved in retinal ganglion cells apoptosis in glaucoma. Thus present study aimed to analyze the association of TNF-α promoter region alterations (c.-238G>A (rs361525), c.-308G>A (rs1800629), c.-857C>T (rs1799724) and c.-863C>A (rs1800630)) with glaucoma in north Indian cohort.METHODS:
Present hospital based case control study involved 286 glaucoma patients (Primary Open Angle Glaucoma [POAG], Primary Angle Closure Glaucoma [PACG], Primary Congenital Glaucoma [PCG]) and 300 controls. TNF-α gene alteration (c.-238G>A (also referred as c.-418G>A; NM_000594.3)), c.-308G>A (c.-488G>A; NM_000594.3), c.-857C>T (c.-1037C>T; NM_000594.3) and c.-863C>A (c.-1043C>A; NM_000594.3) harboring regions were PCR amplified and sequenced by Sanger sequencing. Allele frequency and genotype distribution in glaucoma cases and controls were compared using chi-square test and genetic association tested using different genetic models.RESULTS:
Statistically significant genotype and allelic association was observed between glaucoma cases and controls for c.-308G>A and c.-863C>A alterations (pâ¯=â¯0.001, pâ¯=â¯0.001; pâ¯=â¯0.001, pâ¯=â¯0.001 respectively). AA genotype of c.-308G>A conferred ~7 fold increased risk towards glaucoma (ORâ¯=â¯6.82, 95% CIâ¯=â¯2.82-16.53, pâ¯=â¯0.001). c.-863C>A alteration under dominant, recessive and co-dominant genetic models conferred ~2 fold increased risk for glaucoma. However, no association for c.-238G>A and c.-857C>T variants with glaucoma was observed. Further, three haplotypes (GGCA, GACC and GACA) (ORâ¯=â¯0.48, 95% CIâ¯=â¯0.35-0.67, pâ¯=â¯0.001; ORâ¯=â¯0.58, 95% CIâ¯=â¯0.36-0.91, pâ¯=â¯0.019 and ORâ¯=â¯0.16, 95% CIâ¯=â¯0.05-0.51, pâ¯=â¯0.002, respectively) conferred protective role towards glaucoma.CONCLUSIONS:
Present study is the first to indicate significant association of c.-308G>A and c.-863C>A alterations with glaucoma in cases from north Indian cohort. Also it is the first study from India to analyze the association and interaction of four promoter region alterations (c.-238G>A, c.-308G>A, c.-857C>T and c.-863C>A) in TNF-α resulting in three protective haplotypes.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Glaucoma
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Factor de Necrosis Tumoral alfa
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Polimorfismo de Nucleótido Simple
Tipo de estudio:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
País/Región como asunto:
Asia
Idioma:
En
Revista:
Gene
Año:
2019
Tipo del documento:
Article
País de afiliación:
India