Association of <i>Lysyl oxidase (LOX)</i> polymorphisms with the risk of Keratoconus in an Iranian population

<div><p></p><p><i>Background</i>: Keratoconus is a connective tissue-related eye disease with unknown etiology that causes the loss of visual acuity. Lysyl oxidase (LOX) is an amine oxidase that catalyzes the covalent cross-link of collagens and elastin in the extracellular environment, thus determining the mechanical properties of connective tissue. The current study aimed to investigate the possible associations between two <i>LOX</i> polymorphisms, rs1800449 and rs2288393, and susceptibility to keratoconus.</p><p><i>Methods</i>: A total of 262 Iranian subjects including 112 patients with keratoconus and 150 healthy individuals as controls were recruited. Genotyping for the <i>LOX</i> variants was performed using allele-specific PCR.</p><p><i>Results</i>: A significant difference was found between two groups regarding allelic and genotyping distribution of <i>LOX</i> polymorphism at position rs1800449 G>A. The frequency of AA and GA + AA genotypes were increased in patients compared to controls (17% versus 8% and 62.5% versus 50%, respectively), showing a statistically significant difference (OR = 2.827, 95% CI: 1.251–6.391, <i>p</i> = 0.012). The A allele was associated with an increased risk for keratoconus, with the frequency of 39.9% and 29% in patients and controls, respectively (OR = 1.614, 95% CI: 1.119–2.326, <i>p</i> = 0.011). Furthermore, the haplotype analysis revealed that the rs1800449G/rs2288393C is a protective factor against keratoconus (OR = 0.425, 95% CI = 0.296–0.609, <i>p</i> = 0.001). Conversely, the +473A/rs2288393C (OR = 3.703, 95% CI = 2.230–6.149, <i>p</i> = 0.001) and +473G/rs2288393G (OR = 15.48, 95% CI = 3.805–63.03, <i>p</i> = 0.001) haplotypes were identified as risk factors for keratoconus.</p><p><i>Conclusion</i>: Our study demonstrated that the LOX rs1800449 genotypes (AA and GA + AA) and allele (A) appears to confer risk for susceptibility to keratoconus.</p></div

Association of single nucleotide polymorphisms in AXIN2, BMP4, and IRF6 with Non-Syndromic Cleft Lip with or without Cleft Palate in a sample of the southeast Iranian population

<div><p>Abstract Non-syndromic cleft lip with or without palate (NSCL/P) is a common congenital malformation worldwide, with complex etiology. It has been proposed that interaction of genes and environmental factors play a role in the predisposition to this disease. Objectives: The aim of this study was to examine the association between AXIN2 (axis inhibition protein 2) rs7224837, BMP4 (bone morphogenetic protein 4) rs17563, and IRF6 (interferon regulatory factor 6) rs861019 and 2235371 polymorphisms and NSCL/P in an Iranian population. Material and Methods: This case-control study was carried out on 132 unrelated NSCL/P patients and 156 healthy subjects. The variants were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The findings suggest that BMP4 rs17563 polymorphism significantly decreased the risk of NSCL/P in codominant (OR=0.36, 95%CI=0.17-0.79, p=0.012, CT vs CC and OR=0.11, 95%CI=0.01-0.88, p = 0.019, TT vs CC), dominant (OR=0.30, 95%CI=0.15-0.62, p = 0.0007, CT+TT vs CC), recessive (OR=0.12, 95%CI=0.02-0.99, p = 0.023, TT vs CC+CT), overdominant (OR=0.39, 95%CI = 0.18-0.84, p=0.021, CT vs CC+TT), and allele (OR=0.28, 95%CI=0.15-0.55, p<0.0001, T vs C) inheritance models. Our findings did not support an association between AXIN2 rs7224837 and IRF6 rs861019 polymorphism and risk/protection of NSCL/P. The IRF6 2235371 variant was not polymorphic in our population. Conclusion: The results indicate that the BMP4 rs17563 variant is likely to confer a protective effect against the occurrence of NSCL/P in a sample of the southeast Iranian population.</p></div