Our findings show that the coronary artery disease-associated coding variant rs1051338 causes reduced lysosomal LAL protein and activity because of increased LAL degradation, providing a plausible causal mechanism of increased coronary artery disease risk.
Further, we characterized a second common exonic coding variant (rs1051339), which is predicted to alter LIPA signal peptide cleavage similarly to rs1051338</span>, yet is not linked to intronic variants. rs1051339 also does not impact LIPA function in vitro and confers no coronary artery disease risk.
Our findings show that the coronary artery disease-associated coding variant rs1051338 causes reduced lysosomal LAL protein and activity because of increased LAL degradation, providing a plausible causal mechanism of increased coronary artery disease risk.
Our findings show that the coronary artery disease-associated coding variant rs1051338 causes reduced lysosomal LAL protein and activity because of increased LAL degradation, providing a plausible causal mechanism of increased coronary artery disease risk.
Further, we characterized a second common exonic coding variant (rs1051339), which is predicted to alter LIPA signal peptide cleavage similarly to rs1051338</span>, yet is not linked to intronic variants. rs1051339 also does not impact LIPA function in vitro and confers no coronary artery disease risk.
Further, we characterized a second common exonic coding variant (rs1051339), which is predicted to alter LIPA signal peptide cleavage similarly to rs1051338</span>, yet is not linked to intronic variants. rs1051339 also does not impact LIPA function in vitro and confers no coronary artery disease risk.
We found that LIPA exon 2 polymorphism (rs1051338) influenced plasma 24S-hydroxycholesterol/cholesterol ratios in AD patients where carriers of the C/C allele presented with higher ratios than heterozygote carriers of the LIPA allele.
We investigated two LIPA polymorphisms (rs1051338 and rs2297472) for their putative effect on the risk of LOAD in a homogenous sample of German origin.
We found that LIPA exon 2 polymorphism (rs1051338) influenced plasma 24S-hydroxycholesterol/cholesterol ratios in AD patients where carriers of the C/C allele presented with higher ratios than heterozygote carriers of the LIPA allele.
Further, we characterized a second common exonic coding variant (rs1051339), which is predicted to alter LIPA signal peptide cleavage similarly to rs1051338, yet is not linked to intronic variants. rs1051339 also does not impact LIPA function in vitro and confers no coronary artery disease risk.
Further, we characterized a second common exonic coding variant (rs1051339), which is predicted to alter LIPA signal peptide cleavage similarly to rs1051338, yet is not linked to intronic variants. rs1051339 also does not impact LIPA function in vitro and confers no coronary artery disease risk.
Further, we characterized a second common exonic coding variant (rs1051339), which is predicted to alter LIPA signal peptide cleavage similarly to rs1051338, yet is not linked to intronic variants. rs1051339 also does not impact LIPA function in vitro and confers no coronary artery disease risk.
Meta-analysis of existing genetic studies estimated the prevalence of LAL-D as 1 per 160,000 (95% CI 1 per 65,025-761,652) using the allele frequency of c.894G>A in LIPA.
We used exome sequencing to assess all protein-coding regions of the genome in 3 family members and identified a homozygous exon 8 splice junction mutation (c.894G>A, also known as E8SJM) in LIPA that segregated with the diagnosis of hypercholesterolemia.
CH25H rs13500 polymorphism is associated with an AD risk in the Turkish population and CH25H might have a role in the pathogenesis of AD together with, and independently from APOE.
Additionally, we found the interactions of APOA5 rs662799, BUD13 rs11216129, BUD13 rs623908, CETP rs820299, LIPA rs1412444, alcohol consumption, smoking status, or physical activity on MetS and its individual components.
After age, sex, and BMI adjustment, we observed the SNPs rs12190287, rs12413409, rs1412444, rs1746048 and rs4977574, were significantly associated with MI in additive models and rs12190287, rs12413409, rs4977574 were significantly associated with phenotypes of MI at the same time.
The dosage of serum lysosomal acid lipase was undetectable and we found the presence of a rare homozygous mutation in the gene associated with the lysosomal acid lipase deficiency, (allele c.386A > G homozygous p.H129R).
We investigated two LIPA polymorphisms (rs1051338 and rs2297472) for their putative effect on the risk of LOAD in a homogenous sample of German origin.
The results showed that IL-10 rs304496 was associated with pediatric IBD (<i>P</i> = 0.022), but no association was found for two other IL-10 SNPs, rs1800872 and rs2034498, or for SNPs in genes <i>IL10RA</i>, <i>IL10RB</i>, <i>STAT3</i>, and <i>HO1</i>.
Since the residual LAL activity is higher and the clinical phenotype based on plasma lipid values and severity of hepatosplenomegaly is milder in this case than in a previously studied case who was homozygous for the E8SJM allele, we conclude that the L336P variant appears to be associated with a phenotypically mild form of CESD.