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Genetic association of apolipoprotein E polymorphisms with inflammatory bowel disease.

ABSTRACT: To study the association of apolipoprotein E (APOE) polymorphisms with the susceptibility of inflammatory bowel disease (IBD) in Saudi patients.APOE genotyping was performed to evaluate the allele and genotype frequencies in 378 Saudi subjects including IBD patients with ulcerative colitis (n = 84) or Crohn's disease (n = 94) and matched controls (n = 200) using polymerase chain reaction and reverse-hybridization techniques.The frequencies of the APOE ?2 allele and ?2/?3 and ?2/?4 genotypes were significantly higher in IBD patients than in controls (P < 0.05), suggesting that the ?2 allele and its heterozygous genotypes may increase the susceptibility to IBD. On the contrary, the frequencies of the ?3 allele and ?3/?3 genotype were lower in IBD patients as compared to controls, suggesting a protective effect of APOE ?3 for IBD. The prevalence of the ?4 allele was also higher in the patient group compared to controls, suggesting that the ?4 allele may also increase the risk of IBD. Our results also indicated that the APOE ?4 allele was associated with an early age of IBD onset. No effect of gender or type of IBD (familial or sporadic) on the frequency distribution of APOE alleles and genotypes was noticed in this study.APOE polymorphism is associated with risk of developing IBD and early age of onset in Saudi patients, though further studies with a large-size population are warranted.

SUBMITTER: Al-Meghaiseeb ES

PROVIDER: S-EPMC4299342 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Genetic association of apolipoprotein E polymorphisms with inflammatory bowel disease.

Al-Meghaiseeb Ebtissam Saleh ES Al-Otaibi Mulfi Mubarak MM Al-Robayan Abdulrahman A Al-Amro Reem R Al-Malki Ahmd Saad AS Arfin Misbahul M Al-Asmari Abdulrahman K AK

World journal of gastroenterology 20150101 3

<h4>Aim</h4>To study the association of apolipoprotein E (APOE) polymorphisms with the susceptibility of inflammatory bowel disease (IBD) in Saudi patients.<h4>Methods</h4>APOE genotyping was performed to evaluate the allele and genotype frequencies in 378 Saudi subjects including IBD patients with ulcerative colitis (n = 84) or Crohn's disease (n = 94) and matched controls (n = 200) using polymerase chain reaction and reverse-hybridization techniques.<h4>Results</h4>The frequencies of the APOE ...[more]

PMID: 25624723

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Project description:BackgroundMyeloid cells, including monocytes, macrophages, microglia, dendritic cells and neutrophils are a part of innate immunity, playing a major role in orchestrating innate and adaptive immune responses. Microglia are the resident myeloid cells of the central nervous system, and many Alzheimer's disease (AD) risk loci are found in or near genes that are highly or sometimes uniquely expressed in myeloid cells. Similarly, inflammatory bowel disease (IBD) loci are also enriched for genes expressed by myeloid cells. However, the extent to which there is overlap between the effects of AD and IBD susceptibility loci in myeloid cells remains poorly described, and the substantial IBD genetic maps may help to accelerate AD research.MethodsHere, we leveraged summary statistics from large-scale genome-wide association studies (GWAS) to investigate the causal effect of IBD (including ulcerative colitis and Crohn's disease) variants on AD and AD endophenotypes. Microglia and monocyte expression Quantitative Trait Locus (eQTLs) were used to examine the functional consequences of IBD and AD risk variants enrichment in two different myeloid cell subtypes.ResultsOur results showed that, while PTK2B is implicated in both diseases and both sets of risk loci are enriched for myeloid genes, AD and IBD susceptibility loci largely implicate distinct sets of genes and pathways. AD loci are significantly more enriched for microglial eQTLs than IBD. We also found that genetically determined IBD is associated with a lower risk of AD, which may driven by a negative effect on the accumulation of neurofibrillary tangles (beta=-1.04, p=0.013). In addition, IBD displayed a significant positive genetic correlation with psychiatric disorders and multiple sclerosis, while AD showed a significant positive genetic correlation with amyotrophic lateral sclerosis.ConclusionTo our knowledge, this is the first study to systematically contrast the genetic association between IBD and AD, our findings highlight a possible genetically protective effect of IBD on AD even if the majority of effects on myeloid cell gene expression by the two sets of disease variants are distinct. Thus, IBD myeloid studies may not help to accelerate AD functional studies, but our observation reinforces the role of myeloid cells in the accumulation of tau proteinopathy and provides a new avenue for discovering a protective factor.

Dataset Information

Genetic association of apolipoprotein E polymorphisms with inflammatory bowel disease.

Publications

Genetic association of apolipoprotein E polymorphisms with inflammatory bowel disease.

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