AMD Genetics in India: The Missing Links

Anand, Akshay; Sharma, Kaushal; Sharma, Suresh; Singh, Ramandeep; Sharma, Neel; Prasad, T. S. Keshava

doi:10.3389/fnagi.2016.00115

Cited by 6 publications

(4 citation statements)

References 78 publications

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“…AMD is heterogenic disease and represents the genetic as well as environmental complexity [Anand et al, ]. We have earlier reported the role of angiogenesis [Sharma et al,, ] as well as the role of chemokine and its receptor in AMD pathology in Indian population [Anand et al, ].…”

Section: Discussionmentioning

confidence: 99%

Serum Levels of TIMP-3, LIPC, IER3, and SLC16A8 in CFH-Negative AMD Cases

et al. 2017

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AMD is a complex eye disease predominantly occurring in aged population. Till now about 53 genetic loci have been found to be associated with the AMD pathology. AMD pathogenesis is being increasingly known to progress through mechanisms independent of the CFH mediated pathway. Therefore, our aim for current study was to examine the genes by analyzing their expression levels in AMD. We recruited about 50 AMD and same number of age matched controls. We analyzed the CFH duplication and deletion by multiplex ligation probe amplification (MLPA) and found no duplication and deletion in CFH gene in AMD patients. We also estimated the IER-3, SLC16A8, LIPC, and TIMP-3 expression levels in both CFH-negative AMD cases (i.e. no duplication and deletion in CFH gene) besides examining these in AMD and controls. We found that the expression level of LIPC, SLC16A8, and TIMP-3 was significantly associated with AMD pathology in both groups (LIPC: P = 0.008, SLC16A8: P < 0.001, TIMP-3: P < 0.001, respectively). However, we did not find any significant difference in IER-3 levels in AMD and controls. Therefore, the evidence from current study, suggests that AMD pathology may be mediated through mechanistic pathways linked to other genetic loci. J. Cell. Biochem. 118: 2087-2095, 2017. © 2016 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

Serum Levels of TIMP-3, LIPC, IER3, and SLC16A8 in CFH-Negative AMD Cases

et al. 2017

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“…However, we did not find significant association between number of anti-VEGF injections and such genetic interaction studied in our population. This indicate a complex nature of AMD pathology and associated response of anti-VEGF treatment which can be dependent on the nature of genetic interaction along with contribution of confounders 24 . Moreover, our results have also showed that both APOE and LIPC may act as biomarkers to differentiate degree of anti-VEGF response in wet AMD cases with respect to number of anti-VEGF injection given to the patients.…”

Section: Discussionmentioning

confidence: 99%

Modulated anti-VEGF therapy under the influence of lipid metabolizing proteins in Age related macular degeneration: a pilot study

Sharma

Battu

Singh

et al. 2022

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Age-related macular degeneration (AMD) is a devastating retinal disease that results in irreversible vision loss in the aged population. The complex genetic nature and degree of genetic penetrance require a redefinition of the current therapeutic strategy for AMD. We aimed to investigate the role of modifiers for current anti-VEGF therapy especially for non-responder AMD patients. We recruited 78 wet AMD cases (out of 278 AMD patients) with their socio-demographic and treatment regimen. Serum protein levels were estimated by ELISA in AMD patients. Data pertaining to the number of anti-VEGF injections given (in 1 year) along with clinical images (FFA and OCT) of AMD patients were also included. Visual acuity data (logMAR) for 46 wet AMD cases out of a total of 78 patients were also retrieved to examine the response of anti-VEGF injections in wet AMD cases. Lipid metabolizing genes (LIPC and APOE) have been identified as chief biomarkers for anti-VEGF response in AMD patients. Both genotypes ‘CC’ and ‘GC’ of LIPC have found to be associated with a number of anti-VEGF injections in AMD patients which could influence the expression of B3GALTL,HTRA1, IER3, LIPC and SLC16A8 proteins in patients bearing both genotypes as compared to reference genotype. Elevated levels of APOE were also observed in group 2 wet AMD patients as compared to group 1 suggesting the significance of APOE levels in anti-VEGF response. The genotype of B3GALTL has also been shown to have a significant association with the number of anti-VEGF injections. Moreover, visual acuity of group 1 (≤ 4 anti-VEGF injections/year) AMD patients was found significantly improved after 3 doses of anti-VEGF injections and maintained longitudinally as compared to groups 2 and 3. Lipid metabolising genes may impact the outcome of anti-VEGF AMD treatment.

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“…Disease pathology of AMD is known to be influenced by both genetic and environmental factors evident by our quantitative outcome of protein expression under the influence of environmental factors [1]. In general, the ambiguity in the nature and extent of interaction between environmental and genetic factors has significantly hampered the pace of clinical translation in the field of AMD genetics [2]. Current AMD genetics warrants comprehensive analysis in the manner it can illustrate the contribution and interactions of contributory factors along with their degree of penetrance in disease progression.…”

Section: Discussionmentioning

confidence: 99%

“…Most of the degenerative diseases (e.g. AMD and Alzheimer's disease) have shown complex phenotypes based on both gene-environment interactions which have propensity to alter the cellular functions by gene expression changes [1,2]. AMD is characterized by degenerative changes in macular photoreceptors and vision impairment in elderly.…”

Section: Introductionmentioning

confidence: 99%

Sleeping pattern and activities of daily living modulate protein expression in AMD

et al. 2021

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Degeneration of macular photoreceptors is a prominent characteristic of age-related macular degeneration (AMD) which leads to devastating and irreversible vision loss in the elderly population. In this exploratory study, the contribution of environmental factors on the progression of AMD pathology by probing the expression of candidate proteins was analyzed. Four hundred and sixty four participants were recruited in the study comprising of AMD (n = 277) and controls (n = 187). Genetics related data was analyzed to demonstrate the activities of daily living (ADL) by using regression analysis and statistical modeling, including contrast estimate, multinomial regression analysis in AMD progression. Regression analysis revealed contribution of smoking, alcohol, and sleeping hours on AMD by altered expression of IER-3, HTRA1, B3GALTL, LIPC and TIMP3 as compared to normal levels. Contrast estimate supports the gender polarization phenomenon in AMD by significant decreased expression of SLC16A8 and LIPC in control population which was found to be unaltered in AMD patients. The smoking, food habits and duration of night sleeping hours also contributed in AMD progression as evident from multinomial regression analysis. Predicted model (prediction estimate = 86.7%) also indicated the crucial role of night sleeping hours along with the decreased expression of TIMP-3, IER3 and SLC16A8. Results revealed an unambiguous role of environmental factors in AMD progression mediated by various regulatory proteins which might result in intermittent AMD phenotypes and possibly influence the outcome of anti-VEGF treatment.

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AMD Genetics in India: The Missing Links

Cited by 6 publications

References 78 publications

Serum Levels of TIMP-3, LIPC, IER3, and SLC16A8 in CFH-Negative AMD Cases

Serum Levels of TIMP-3, LIPC, IER3, and SLC16A8 in CFH-Negative AMD Cases

Modulated anti-VEGF therapy under the influence of lipid metabolizing proteins in Age related macular degeneration: a pilot study

Sleeping pattern and activities of daily living modulate protein expression in AMD

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