Affiliations: Biochemistry Laboratory, School of Environmental
Sciences, Jawaharlal Nehru University, New Delhi, India | Dristi Pradip, Jodhpur Park, Kolkata, India | Molecular and Human Genetics Division, CSIR-Indian
Institute of Chemical Biology, Kolkata, India | Genomics and Molecular Medicine, CSIR-Institute of
Genomics and Integrative Biology, Delhi, India
Note: [] Corresponding authors: Dr. Arijit Mukhopadhyay, Genomics and
Molecular Medicine, CSIR-Institute of Genomics and Integrative Biology, Mall
Road, Delhi 110007, India. Tel.: +91 11 27666156 (extn 121); Fax: +91 11
27667471; E-mail: [email protected], [email protected]. Dr. Kasturi Datta,
Genomics and Molecular Medicine, CSIR-Institute of Genomics and Integrative
Biology, Mall Road, Delhi 110007, India. Tel.: +91 11 27666156 (extn 121); Fax:
+91 11 27667471; E-mail: [email protected], [email protected]
Abstract: Hyaluronan (HA) plays a significant role in maintaining aqueous
humor outflow in trabecular meshwork, the primary ocular tissue involved in
glaucoma. We examined potential association of the single nucleotide
polymorphisms (SNPs) of the HA synthesizing gene – hyaluronan synthase 2
(HAS2), hyaluronan binding protein 1 (HABP1) and HA catabolic gene
hyaluronidase 3 (HYAL3) in the primary open angle glaucoma (POAG) patients in
the Indian population. Thirteen tagged SNPs (6 for HAS2, 3 for HABP1 and 4 for
HYAL3) were genotyped in 116 high tension (HTG), 321 non-high tension glaucoma
(NHTG) samples and 96 unrelated, age-matched, glaucoma-negative, control
samples. Allelic and genotypic association were analyzed by PLINK v1.04;
haplotypes were identified using PHASE v2.1 and gene-gene interaction was
analyzed using multifactor dimensionality reduction (MDR) v2.0. An allelic
association (rs6651224; p= 0.03; OR: 0.49; 95% CI: 0.25–0.94) was
observed at the second intron (C>G) of HAS2 both for NHTG and HTG. rs1057308
revealed a genotypic association (p=0.03) at the 5' UTR of HAS2 with only HTG.
TCT haplotype (rs1805429 – rs2472614 – rs8072363) in HABP1 and TTAG
and TTGA (rs2285044 – rs3774753 – rs1310073 – rs1076872) in
HYAL3 were found to be significantly high (p< 0.05) both for HTG and NHTG
compared to controls. Gene-gene interaction revealed HABP1 predominantly
interacts with HAS2 in HTG while it associates with both HYAL3 and HAS2 in
NHTG. This is the first genetic evidence, albeit from a smaller study, that the
natural polymorphisms in the genes involved in hyaluronan metabolism are
potentially involved in glaucomatous neurodegeneration.
