title: Genetic association of SNPs near ATOH7, CARD10, CDKN2B, CDC7 and SIX1/SIX6 with the endophenotypes of primary open angle glaucoma in Indian population.
abstract: Primary open angle glaucoma (POAG) belonging to a group of optic neuropathies, result from interaction between genetic and environmental factors. Study of associations with quantitative traits (QTs) is one of the successful strategies to understand the complex genetics of POAG. The current study attempts to explore the association of variations near/in genes like ATOH7, SIX1/SIX6 complex, CDKN2B, CARD10, and CDC7 with POAG and its QTs including vertical cup to disc ratio (VCDR), central corneal thickness (CCT), intra ocular pressure (IOP), and axial length (AL). Case-control study design was carried out in a sample size of 97 POAG cases and 371 controls from South India. Model-based (additive, recessive, dominant) association of the genotypes and their interaction was carried out between cases and controls using chi-square, linear and logistic regression methods. Nominal significance (P<0.05) was observed for QTs like i) VCDR with SNPs rs1900004 (ATOH7); rs1192415 (CDC7); rs10483727 (SIX1/SIX6), rs9607469 (CARD10); ii) CCT with rs1192415; iii) IOP with rs1900004 and iv) AL with rs1900004 and rs1063192 (CDKN2B). We were able to replicate previously known interactions between ATOH7-SIX6 and SIX6-CDKN2B along with few novel interactions between ATOH7-CDC7 and SIX6 with genes including CARD10 and CDC7. In summary, our results suggest that a probable interaction among the candidate genes for QTs, play a major role in determining the individual's susceptibility to POAG.
authors: SNONGC Department of Genetics and Molecular biology, Vision Research foundation, Sankara Nethralaya, Chennai, India; PhD Scholar, Birla Institute of Technology & Science (BITS), Pilani, 333 031, Rajasthan, India.
authors: Ferdinamarie Sharmila
authors: FS
authors: Philomenadin
authors: Chennai Glaucoma Study, Medical and Vision Research Foundation, Sankara Nethralaya, Chennai, India.
authors: Rashima
authors: R
authors: Asokan
authors: Biostatistician, Department of Preventive Ophthalmology, Medical research foundation, Sankara Nethralaya, Chennai, India.
authors: Viswanathan
authors: V
authors: N
authors: Chennai Glaucoma Study, Medical and Vision Research Foundation, Sankara Nethralaya, Chennai, India.
authors: Ronnie
authors: R
authors: George
authors: Chennai Glaucoma Study, Medical and Vision Research Foundation, Sankara Nethralaya, Chennai, India.
authors: Vijaya
authors: V
authors: Lingam
authors: SNONGC Department of Genetics and Molecular biology, Vision Research foundation, Sankara Nethralaya, Chennai, India.
authors: Sripriya
authors: S
authors: Sarangapani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics*; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics*; D058068:Endophenotypes; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D053468:CARD Signaling Adaptor Proteins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D018398:Homeodomain Proteins; D017346:Protein Serine-Threonine Kinases; D015534:Trans-Activators; C456975:ATOH7 protein, human; C430880:CARD10 protein, human; C493966:CDKN2B protein, human; C099236:SIX1 protein, human; C491945:SIX6 protein, human; C068619:CDC7 protein, human