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Chromosome 19p13 loci in Finnish migraine with aura families
Author(s) -
Kaunisto Mari A.,
Tikka Päivi J.,
Kallela Mikko,
Leal Suzanne M.,
Papp Jeanette C.,
Korhonen Arja,
Hämäläinen Eija,
Harno Hanna,
Havanka Hannele,
Nissilä Markku,
Säkö Erkki,
Ilmavirta Matti,
Kaprio Jaakko,
Färkkilä Markus,
Ophoff Roel A.,
Palotie Aarno,
Wessman Maija
Publication year - 2004
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.30082
Subject(s) - locus (genetics) , migraine with aura , genetics , migraine , genetic linkage , aura , chromosomal region , biology , candidate gene , gene , medicine
Abstract Chromosomal area 19p13 contains two migraine associated genes: a Ca v 2.1 (P/Q‐type) calcium channel α 1 subunit gene, CACNA1A , and an insulin receptor gene, INSR . Missense mutations in CACNA1A cause a rare Mendelian form of migraine, familial hemiplegic migraine type 1 (FHM1). Contribution of CACNA1A locus has also been studied in the common forms of migraine, migraine with (MA) and without aura (MO), but the results have been contradictory. The role of INSR is less well established: A region on 19p13 separate from CACNA1A was recently reported to be a major locus for migraine and subsequently, the INSR gene was associated with MA and MO. Our aim was to clarify the role of these loci in MA families by analyzing 72 multigenerational Finnish MA families, the largest family sample so far. We hypothesized that the potential major contribution of the 19p13 loci should be detected in a family sample of this size, and this was confirmed by simulations. We genotyped eight polymorphic microsatellite markers surrounding the INSR and CACNA1A genes on 757 individuals. Using parametric and non‐parametric linkage analysis, none of the studied markers showed any evidence of linkage to MA either under locus homogeneity or heterogeneity. However, marginally positive lod scores were observed in three families, and thus for these families the results remain inconclusive. The overall conclusion is that our study did not provide evidence of a major MA susceptibility region on 19p13 and thus we were not able to replicate the INSR locus finding. © 2004 Wiley‐Liss, Inc.