Population variation in linkage disequilibrium across the COMT gene considering promoter region and coding region variation

被引:67
作者
DeMille, MMC
Kidd, JR
Ruggeri, V
Palmatier, MA
Goldman, D
Odunsi, A
Okonofua, F
Grigorenko, E
Schulz, LO
Bonne-Tamir, B
Lu, RB
Parnas, J
Pakstis, AJ
Kidd, KK [1 ]
机构
[1] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA
[2] NIAAA, Neurogenet Lab, Rockville, MD 20852 USA
[3] New York State Dept Hlth, Roswell Pk Mem Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA
[4] Univ Benin, Fac Med, Dept Obstet & Gynecol, Benin, Nigeria
[5] Yale Univ, Dept Psychol, New Haven, CT 06511 USA
[6] Univ Wisconsin, Dept Hlth Sci, Milwaukee, WI 53201 USA
[7] Tel Aviv Univ, Sackler Sch Med, Dept Genet, IL-69978 Tel Aviv, Israel
[8] Tri Serv Gen Hosp, Natl Def Med Ctr, Dept Psychiat, Taipei, Taiwan
[9] Univ Copenhagen, Hvidovre Hosp, Dept Psychiat, DK-2650 Hvidovre, Denmark
关键词
D O I
10.1007/s00439-002-0809-0
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Catechol-O-methyl transferase (COMT) catalyzes the first step in one of the major pathways in the degradation of catecholamines. The COMT gene on chromosome 22 has been considered a candidate gene for many neuropsychiatric disorders, in part because an exon 4 single nucleotide polymorphism (SNP) in COMT causes an amino acid substitution associated with significantly altered enzyme activity. This functional variant, detected as an NlaIII restriction site polymorphism (RSP), is polymorphic in populations from around the world. A four-site haplotype spanning 28 kb effectively encompasses COMT. This haplotype is comprised of two novel polymorphisms [a tetranucleotide short tandem repeat polymorphism (STRP) in intron I and a HindIII RSP at the 5' end of COMT], the NlaIII site, and another previously published site - a Bg/I RSP at the 3' end of the gene. Overall linkage disequilibrium (LD) for this haplotype is strong and significant in 32 population samples from around the world. Conditional probabilities indicate that, in spite of moderate to strong disequilibrium in most non-African populations, the NlaIII site, although often used for prediction, would not always be a reliable predictor of allelic variation at the other sites. Because other functional variation might exist, especially regulatory variation, these findings indicate that haplotypes would be more effective indicators of possible involvement of COMT in disease etiology.
引用
收藏
页码:521 / 537
页数:17
相关论文
共 32 条
  • [21] Linkage disequilibrium at the ADH2 and ADH3 loci and risk of alcoholism
    Osier, M
    Pakstis, AJ
    Kidd, JR
    Lee, JF
    Yin, SJ
    Ko, HC
    Edenberg, HJ
    Lu, RB
    Kidd, KK
    [J]. AMERICAN JOURNAL OF HUMAN GENETICS, 1999, 64 (04) : 1147 - 1157
  • [22] Global variation in the frequencies of functionally different catechol-O-methyltransferase alleles
    Palmatier, MA
    Kang, AM
    Kidd, KK
    [J]. BIOLOGICAL PSYCHIATRY, 1999, 46 (04) : 557 - 567
  • [23] CATECHOL-O-METHYLTRANSFERASE ACTIVITY - A DETERMINANT OF LEVODOPA RESPONSE
    REILLY, DK
    RIVERACALIMLIM, L
    VANDYKE, D
    [J]. CLINICAL PHARMACOLOGY & THERAPEUTICS, 1980, 28 (02) : 278 - 286
  • [24] CONTRIBUTION OF SULFATE CONJUGATION, DEAMINATION, AND O-METHYLATION TO METABOLISM OF DOPAMINE AND NOREPINEPHRINE IN HUMAN-BRAIN
    RIVETT, AJ
    EDDY, BJ
    ROTH, JA
    [J]. JOURNAL OF NEUROCHEMISTRY, 1982, 39 (04) : 1009 - 1016
  • [25] DISTINCT CELLULAR-LOCALIZATION OF MEMBRANE-BOUND AND SOLUBLE FORMS OF CATECHOL-O-METHYLTRANSFERASE IN BRAIN
    RIVETT, AJ
    FRANCIS, A
    ROTH, JA
    [J]. JOURNAL OF NEUROCHEMISTRY, 1983, 40 (01) : 215 - 219
  • [26] Sambrook J., 2002, MOL CLONING LAB MANU
  • [27] GENOMIC ORGANIZATION OF THE HUMAN CATECHOL O-METHYLTRANSFERASE GENE AND ITS EXPRESSION FROM 2 DISTINCT PROMOTERS
    TENHUNEN, J
    SALMINEN, M
    LUNDSTROM, K
    KIVILUOTO, T
    SAVOLAINEN, R
    ULMANEN, I
    [J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1994, 223 (03): : 1049 - 1059
  • [28] Soluble and membrane-bound catechol-O-methyltransferase in normal and malignant mammary gland
    Tenhunen, J
    Heikkilä, P
    Alanko, A
    Heinonen, E
    Akkila, J
    Ulmanen, I
    [J]. CANCER LETTERS, 1999, 144 (01) : 75 - 84
  • [29] A global haplotype analysis of the myotonic dystrophy locus: Implications for the evolution of modern humans and for the origin of myotonic dystrophy mutations
    Tishkoff, SA
    Goldman, A
    Calafell, F
    Speed, WC
    Deinard, AS
    Bonne-Tamir, B
    Kidd, JR
    Pakstis, AJ
    Jenkins, T
    Kidd, KK
    [J]. AMERICAN JOURNAL OF HUMAN GENETICS, 1998, 62 (06) : 1389 - 1402
  • [30] Weir B. S., 1996, GENETIC DATA ANAL