Lack of association of Lysyl oxidase (LOX) gene polymorphisms with intracranial aneurysm in a south Indian population

Abstract

Intracranial aneurysm (IA) accounts for 85 % of haemorrhagic stroke and is mainly caused due to weakening of arterial wall. Lysyl oxidase (LOX) is a cuproenzyme involved in cross linking structural proteins collagen and elastin, thus providing structural stability to artery. Using a case-control study design, we tested the hypothesis whether the variants in LOX gene flanking the two LD block, can increase risk of aSAH among South Indian patients, either independently, or by interacting with other risk factors of the disease. SNPs were genotyped by fluorescence-based competitive allele-specific PCR (KASPar) chemistry. We selected 200 radiologically confirmed aneurysmal cases and 235 ethnically and age and gender matched controls from the Dravidian Malayalam speaking population of South India. We observed marked interethnic differences in the genotype distribution of LOX variants when compared to Japanese and African populations. However, there was no significant association with any of the LOX variants with IA. This study also could not observe any significant role of LOX polymorphisms in influencing IA either directly or indirectly through its confounding factors such as hypertension and gender in South Indian population.

Association of Versican (VCAN) gene polymorphisms rs251124 and rs2287926 (G428D), with intracranial aneurysm

“…Reduced extracellular matrix is a prominent feature of cerebral aneurysms. In an earlier study we reported that lysyl oxidase (LOX) is an enzyme which is involved in covalent cross linking of these fibrous proteins by the formation of aldehydes between lysine residues that insolubilize these extracellular proteins namely collagen and elastin ( Kagan and Li, 2003 ), thus giving strength to intracranial arteries was not found to be associated with IA in our study population ( Sathyan et al, 2013 ). Proteoglycan Versican ( VCAN ) is a putative candidate gene for IAs as it plays an important role in extracellular matrix assembly and is localized near a previously implicated locus for IAs on chromosome 5q22–31 ( Onda et al, 2001 ).…”

A Novel Association between Lysyl Oxidase Gene Polymorphism and Intracranial Aneurysm in Koreans

“…They reported that serpine 1 ( SERPINE 1, combined OR 1.27, p =0.004), FBN2 (combined OR 1.37, p =0.01), and alpha 1 type IV collagen ( COL4A1 , combined OR 1.22, p =0.007) were related to IA; however, no association of SNPs between the LOX gene and IA was demonstrated. Sathyan, et al 7 did not find allelic or genotypic variants of the LOX gene in a South Indian population with IA. Several genome-wide association studies 26 27 also did not demonstrate the 5q22-31 loci for IA formation.…”

“…In addition, no significant associations of LOX variants with IA were observed in a South Indian population. 7 Nevertheless, LOX has been reported to be a risk factor for coronary artery disease (CAD) and cerebral stroke. Ma, et al 8 found that G473A polymorphism of LOX was associated with CAD.…”

Polymorphisms in Lysyl Oxidase Family Genes Are Associated With Intracranial Aneurysm Susceptibility in a Chinese Population

“…also found that the C allele of LOX rs3900446 and the G allele of rs763497 with increased risk of IA (OR, 20.15; P = 4.8 × 10 -5 and OR, 2.26; P = 4.8 × 10 -5 ) in Korean population, respectively ( 25 ). However, the polymorphisms of LOX gene is not associated with IA in Japanese and Dutch ( 23 ), central European ( 22 ) and South Indian ( 24 ) populations. Lan Ma et al.…”

“…So far, few population studies have explored associations between polymorphisms in LOX family genes and IA, and the results were inconsistent. For instance, associations between LOX gene polymorphisms and IA have not been found in Japanese, Central European, and South Indian populations ( 22 – 24 ). However, a recent population study in Korea found three SNPs of LOX (rs2303656, rs3900446, and rs763497) were significantly associated with IA (maximum OR, 20.15; P = 4.8 × 10 –5 ) ( 25 ).…”