Chromosome 19 locus apolipoprotein C-II association with multiple sclerosis

Zouali, Hamed; Faure-Delanef, Laurence; Lucotte, G.

doi:10.1177/135245859900500211

Cited by 13 publications

(4 citation statements)

References 11 publications

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“…At this point, we should mention that the high diversity of the compound STR (TG) n (AG) m rs139985133 is remarkable. Although it presented significant differences in allele frequencies, the range of repeats detected in Bolivians was quite similar to that found in our European population and in a French sample (Zouali et al, 1999). The sequencing of five individuals in this study confirmed a previous report that diversity at this locus is attributable to variation at both (TG) n and (AG) m motifs (Fornage et al, 1992).…”

Section: Discussionsupporting

confidence: 87%

Apolipoprotein E/C1/C4/C2 Gene Cluster Diversity in Two Native Andean Populations: Aymaras and Quechuas

Gayà-Vidal

Athanasiadis

Carreras‐Torres

et al. 2012

Annals of Human Genetics

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SummaryThe APOE/C1/C4/C2 gene cluster presents high relevance in lipid metabolism and, therefore, has important epidemiological implications. Here, we study for the first time the variation patterns of 25 polymorphisms (10 short tandem repeats, STRs, and 15 single nucleotide polymorphismas, SNPs) in two native Andean samples from Bolivia (45 Aymaras and 45 Quechuas) as well as one European sample (n = 41) as external reference. We estimated diversity parameters, linkage disequilibrium patterns, population structure, and possible selective effects. In general, diversity was low and could be partly attributed to selection (probably due to its physiological importance), since the APOE/C1/C4/C2 region was highly conserved compared to the flanking genes in both Bolivians and Europeans. Moreover, the lower gene diversity in Bolivians compared to Europeans for some markers might indicate different demographic histories. Regarding the APOE isoforms, in addition to ε3 (94%) and ε4 (5%), isoform ε2 (1%) was also detected in Bolivians. In relation to previous hypotheses, our results support that genetic drift or founder effects rather than selection for increased cholesterol absorption are the main factors that have shaped the distribution of APOE isoforms observed in South America.

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Section: Discussionsupporting

confidence: 87%

Apolipoprotein E/C1/C4/C2 Gene Cluster Diversity in Two Native Andean Populations: Aymaras and Quechuas

Gayà-Vidal

Athanasiadis

Carreras‐Torres

et al. 2012

Annals of Human Genetics

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“…Three other genomic screens (Ebers et al 1996;Sawcer et al 1996;Kuokkanen et al 1997) have shown some support for linkage to this region, and a meta-analysis of all four genomic screens (Wise et al 1999) identified 19q13 as the second-mostsignificant region after the MHC. Additional evidence for this region came from allelic association studies (Barcellos et al 1997;Zouali et al 1999;D'Alfonso et al 2000) and, more recently, from follow-up analyses by the Multiple Sclerosis Genetics Group (MSGG) in both North American (Pericak- and San Marinese populations (Haines et al 2000). As with most complex diseases, the data are not entirely consistent; not all studies have shown evidence of linkage (Chataway et al 1998;D'Alfonso et al 1999), and association results were based on polymorphisms in different markers.…”

Section: Introductionmentioning

confidence: 99%

Association of Polymorphisms in the Apolipoprotein E Region with Susceptibility to and Progression of Multiple Sclerosis

Schmidt

Barcellos

DeSombre

et al. 2002

The American Journal of Human Genetics

116

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Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, with a complex etiology that includes a strong genetic component. The contribution of the major histocompatibility complex (MHC) has been established in numerous genetic linkage and association studies. In addition to the MHC, the chromosome 19q13 region surrounding the apolipoprotein E (APOE) gene has shown consistent evidence of involvement in MS when family-based analyses were conducted. Furthermore, several clinical reports have suggested that the APOE-4 allele may be associated with more-severe disease and faster progression of disability. To thoroughly examine the role of APOE in MS, we genotyped its functional alleles, as well as seven single-nucleotide polymorphisms (SNPs) located primarily within 13 kb of APOE, in a data set of 398 families. Using family-based association analysis, we found statistically significant evidence that an SNP haplotype near APOE is associated with MS susceptibility (P=.005). An analysis of disease progression in 614 patients with MS from 379 families indicated that APOE-4 carriers are more likely to be affected with severe disease (P=.03), whereas a higher proportion of APOE-2 carriers exhibit a mild disease course (P=.02).

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“…10 It is coded for by a 3.7-kbp gene on chromosome 19, in close proximity to the Apo-CII locus, which has been implicated in MS susceptibility in one study. 11 Apo-E is found in chylomicra and VLDL and also in the HDLc, HDL 2 , and b-VLDL lipoprotein remnant complexes. It exhibits specificity for the Apo-B/E receptor, which is expressed in liver, macrophage, astrocyte and oligodendrocyte cells, amongst others.…”

Section: Introductionmentioning

confidence: 99%

Interferon-β-1b and interferon-γ have similar inhibitory effects on apolipoprotein-E production in the monocyte/macrophage

O'Toole

Love

2002

Mult Scler

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Apolipoprotein-E (Apo-E) is the major lipid carrier in the brain, and is therefore important in the recyding of lipids and cholesterol to regenerating neurons during the remission phase of multiple sclerosis (MS). Interferon (IFN)-gamma has been shown to inhibit Apo-E production by a mainly post-transcriptional method in a macrophage cell line, and reduced Apo-E in cerebrospinal fluid is noted during the remission phase in patients. IFN-beta-1b is a recombinantly produced, anti-inflammatory cytokine, which has been shown to reduce the severity of MS relapses and reduce relapse rate. We have examined the effects of IFN-gamma and IFN-beta-1b on the production of Apo-E mRNA, cellular protein and secreted protein in primary monocytes derived from donor blood. IFN-beta-1b does not relieve the dose-dependent inhibition of Apo-E seen with IFN-gamma at up to 100 U/ml in these cells, and when used alone inhibits Apo-E production in a dose-dependent manner. This inhibition by IFN-beta-1b was seen to be at a transcriptional level, and dose dependent up to 100 U/ml. Apo-E genotype, which has also been linked to failure to recover from MS relapses, did not affect this inhibition. The mode of action of IFN-beta-1b in MS is therefore not thought to be through modification of Apo-E production.

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Chromosome 19 locus apolipoprotein C-II association with multiple sclerosis

Cited by 13 publications

References 11 publications

Apolipoprotein E/C1/C4/C2 Gene Cluster Diversity in Two Native Andean Populations: Aymaras and Quechuas

Apolipoprotein E/C1/C4/C2 Gene Cluster Diversity in Two Native Andean Populations: Aymaras and Quechuas

Association of Polymorphisms in the Apolipoprotein E Region with Susceptibility to and Progression of Multiple Sclerosis

Interferon-β-1b and interferon-γ have similar inhibitory effects on apolipoprotein-E production in the monocyte/macrophage

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