Abstract | BACKGROUND: Chromosome 22q13 has shown linkage with schizophrenia (SCZ) and bipolar affective disorder (BPAD). A missense mutation in MLC1 (putative cation-channel gene on 22q13) co-segregating with periodic catatonic schizophrenia has been reported. We have investigated the relationship of MLC1 with SCZ and BPAD in Southern India. METHODS: All exons and flanking intronic sequences of MLC1 were screened for novel variations. Case-control (216 BPAD, 193 SCZ, 116 control subjects) and family-based analyses (113 BPAD, 107 SCZ families) were performed to evaluate association of MLC1 with these disorders. RESULTS: We found 33 MLC1 sequence variations, including three novel mutations: Val210Ile, Leu308Gln, and Arg328His in six BPAD cases and Val210Ile in one control individual. Minor allele of a common variation, ss16339182 (in approximately 6 Kb Linkage-Disequilibrium [LD]-block) was associated with BPAD in case-control (p = .03) and family-based analyses (transmitted/nontransmitted [T/NT]-44/20; p = .003). Association was observed for rs2235349 and rs2076137 with SCZ and ss16339163 with BPAD in case-control study. Using Block 2 haplotype tagging single nucleotide polymorphisms (htSNPs), GC haplotype revealed association (p = .02) and excess transmission (p = .002) with BPAD. CONCLUSIONS: Association of MLC1 with SCZ and BPAD suggests involvement of a common pathway. Rare missense mutations and common variants associated with BPAD favors hypothesis about likely involvement of both rare and common polymorphisms in etiology of this complex disorder.
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Authors | Ranjana Verma, Mitali Mukerji, Deepak Grover, Chandrika B-Rao, Swapan Kumar Das, Shobana Kubendran, Sanjeev Jain, Samir K Brahmachari |
Journal | Biological psychiatry
(Biol Psychiatry)
Vol. 58
Issue 1
Pg. 16-22
(Jul 01 2005)
ISSN: 0006-3223 [Print] United States |
PMID | 15992519
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- MLC1 protein, human
- Membrane Proteins
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Topics |
- Adult
- Bipolar Disorder
(epidemiology, genetics)
- Case-Control Studies
- Chromosomes, Human, Pair 22
(genetics)
- Female
- Gene Frequency
- Genetic Variation
- Genotype
- Haplotypes
- Humans
- India
(epidemiology)
- Linkage Disequilibrium
(genetics)
- Male
- Membrane Proteins
(genetics)
- Mutation, Missense
- Polymorphism, Single Nucleotide
(genetics)
- Schizophrenia
(epidemiology, genetics)
- Schizophrenia, Catatonic
(genetics)
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