Chromosome-12 mapping of late-onset Alzheimer disease among Caribbean Hispanics - PubMed (original) (raw)

doi: 10.1086/324773. Epub 2001 Nov 19.

J H Lee, S N Romas, D Mayo, V Santana, J Williamson, A Ciappa, H Z Rondon, P Estevez, R Lantigua, M Medrano, M Torres, Y Stern, B Tycko, J A Knowles

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Chromosome-12 mapping of late-onset Alzheimer disease among Caribbean Hispanics

R Mayeux et al. Am J Hum Genet. 2002 Jan.

Abstract

Linkage to chromosome 12p for familial Alzheimer disease (AD) has been inconsistent. Using 35 markers near the centromere of chromosome 12, we investigated 79 Caribbean Hispanic families with AD. Two-point linkage analysis using affected sib pairs yielded LOD scores of 3.15 at D12S1623 and 1.43 at D12S1042. The LOD score at D12S1623 decreased to 1.62 in families with late-onset (age >65 years) AD (LOAD), but the LOD score at D12S1042 was unchanged. Among families negative for the apolipoprotein E (APOE-epsilon 4) allele, the LOD score for D12S1623 was lower (1.01), whereas that for D12S1042 increased to 1.73. Among families positive for the APOE-epsilon 4 allele, none of the LOD scores reached 1. Multipoint affected-relative-pair analysis showed peaks at D12S1623 (nonparametric linkage [NPL] score 1.52; P=.028) and near D12S1042, at D12S1057 (NPL score 1.57; P=.027). NPL scores for both D12S1623 and D12S1057 increased in families affected with LOAD, but, in APOE-epsilon 4-negative families, only scores for the region flanking D12S1623 remained elevated (NPL score 1.74; P=.013). This study of Caribbean Hispanics with familial AD extends and provides modest evidence of linkage to loci on chromosome 12p. Linkage varied by age at onset of AD and by the presence or absence of the APOE-epsilon 4 allele.

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Figures

Figure 1

Figure 1

Results of the two-point analysis showing linkage for markers D12S1623 (LOD 3.15) and D12S1042 (LOD 1.43) on chromosome 12. The two markers are ∼30 cM apart. The upper graph shows the results overall and when restricted by age at onset >65 years. The lower graph shows the results stratified by the presence or absence of an APOE-ε4 allele.

Figure 2

Figure 2

Results of multipoint affected-relative-pair analyses, showing peaks near the same two markers, D12S1623 (NPL score 1.52;

_P_=.028

) and D12S1057 (NPL score 1.57;

_P_=.027

). Among late-onset families, the NPL score for D12S1623 was 2.01 (

_P_=.006

), whereas that for D12S1057 was 1.63 (

_P_=.021

). The upper graph shows the results overall and when restricted by age at onset >65 years. The lower graph shows the results stratified by the presence or absence of an APOE-ε4 allele.

References

Electronic-Database Information

    1. Genome Database, The, http://www.gdb.org/
    1. Marshfield Medical Research Foundation, Center for Medical Genetics, http://research.marshfieldclinic.org/genetics/
    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/ (for AD [MIM 104300], AD5 [MIM 602096], APOE-ε4 [MIM 107741], Lewy body dementia [MIM 127750], A2M [MIM 103950], and LRP1 [MIM 107770])

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