The SPARC-related modular calcium binding protein 2 (<em>SMOC2</em>) gene polymorphism in primary glaucoma: a case-control study

Abstract

Primary glaucomas are among the most common eye diseases that may potentially result in bilateral blindness. Both genetics and environmental factors are reported to be involved in the etiology of primary glaucomas. Secreted protein acidic and rich in cysteine (SPARC)-related modular calcium binding protein 2 (SMOC2) is a matricellular glycoprotein encoded by the SMOC2 gene and known to regulate the expression of extracellular matrix (ECM) proteins and matrix metalloproteinases (MMPs), which play an important role in the pathogenesis of primary glaucomas. The frequencies of alleles and genotypes of SMOC2 variants were examined in 406 Saudi subjects, including primary open angle glaucoma (POAG, n=140) and primary angle closure glaucoma (PACG, n=64) patients and 202 matched healthy controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Genotyping of SMOC2 polymorphism (rs13208776) revealed a significantly higher frequency of the heterozygous genotype GA (P<0.01) and a lower frequency of wild type GG genotype (P=0.05) in glaucoma patients compared to the controls. Upon stratification of the patients on the basis of types of glaucoma, PACG patients had a significantly higher frequency of GA genotype as compared to the controls (P<0.01), whereas there was no significant difference between the POAG patient and control groups in frequencies of SMOC2 alleles and genotypes. Further, there was no significant difference in frequency distribution of alleles and genotypes between male and female patients. This study indicates that the GA genotype of SMOC2 (G>A) polymorphism is significantly associated with PACG and may be a risk factor. However, further large-scale studies in the Saudi population as well as in other ethnic populations are needed to confirm this association.

Molecular Genetics of Glaucoma: Subtype and Ethnicity Considerations

“…The eNOS polymorphism was also found to be associated with POAG [ 58 ]. In 2017, a case-control study associated the GA genotype of the SMOC2 (G > A) polymorphism with PACG in a SA population [ 162 ]. Additionally, in 2020 a SNP in the ACVR1 gene involved in the bone morphogenic protein (BMP) signaling pathway was associated with both PACG and PXG in a SA cohort [ 152 ].…”

SMOC2, an intestinal stem cell marker, is an independent prognostic marker associated with better survival in colorectal cancers

“…For instance, SMOC2 polymorphism has been associated with autoimmune diseases, such as generalized vitiligo and autoimmune thyroid disease 7 , 8 . Furthermore, SMOC2 (G>A) polymorphism was reported to be significantly associated with primary glaucoma 9 . Additionally, SMOC2 mutations have been identified in several dental disorders, including a severe developmental dental defect 10 and oligodontia and microdontia 11 .…”

Matricellular Protein Levels in Aqueous Humor and Surgical Outcomes of Trabeculectomy

“…14 They were found widely expressed in all kinds of glaucomatous eyes, and the overexpression of these proteins was noted to add ECM turnover. 5,15,16 Our previous study showed that the levels of matricellular proteins, including SPARC, TSP-2, and osteopontin, were significantly elevated in eyes that suffered from acute angle closure. 4 This elevation might lead to the ECM remodeling and subsequent outflow pathway occlusion.…”