Abstract
ITIH3 and ITIH4 are involved in the stabilization of the extracellular matrix. Several genome-wide association studies and case–control studies regarding psychiatric disorders have identified ITIH3 and ITIH4 single nucleotide polymorphisms (SNPs). The present case–control study examined the relationship between ITIH3 SNPs rs2535629 and rs736408 and ITIH4 SNPs rs3821831 and rs2239547 and depressive symptoms during pregnancy in Japan. Cases comprised 273 women with depressive symptoms during pregnancy defined as a Center for Epidemiological Studies Depression Scale (CES-D) score ≥ 16. Control subjects comprised 1176 women without depressive symptoms during pregnancy, according to the CES-D criteria, who had not been diagnosed with depression by a doctor. Adjustment was made for age, gestation at baseline, region of residence, the presence of children, family structure, smoking, employment, and education. Compared with the TT genotype of ITIH4 SNP rs2239547, the CC genotype was significantly related to a reduced risk of depressive symptoms during pregnancy: the adjusted odds ratio (95% CI) was 0.84 (0.63–1.11) for the TC genotype and 0.57 (0.36–0.91) for the CC genotype. ITIH3 SNPs rs2535629 and rs736408 and ITIH4 SNP rs3821831 were not related to depressive symptoms during pregnancy. The GCCT haplotype of rs2535629, rs736408, rs3821831, and rs2239547 was significantly positively associated with depressive symptoms during pregnancy. A significant interaction was found between rs2239547 and the presence of children. This is the first study to show significant associations of ITIH4 SNP rs2239547 and the GCCT haplotype with depressive symptoms during pregnancy. The effect of the presence of children might depend on rs2239547.
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Acknowledgements
This study was supported by JSPS KAKENHI Grant numbers 19590606JP, 20791654JP, 21590673JP, 22592355JP, 22119507JP, 24390158JP, 25463275JP, 25670305JP, 17K12011JP, and 17H04135JP and by Health and Labour Sciences Research Grants for Research on Allergic Disease and Immunology and Health Research on Children, Youth and Families from the Ministry of Health, Labour and Welfare, Japan. The authors would like to thank the Kyushu Branch of the Japan Allergy Foundation, the Fukuoka Association of Obstetricians and Gynecologists, the Okinawa Association of Obstetricians and Gynecologists, the Miyazaki Association of Obstetricians and Gynecologists, the Oita Association of Obstetricians and Gynecologists, the Kumamoto Association of Obstetricians and Gynecologists, the Nagasaki Association of Obstetricians and Gynecologists, the Kagoshima Association of Obstetricians and Gynecologists, the Saga Association of Obstetricians and Gynecologists, the Fukuoka Society of Obstetrics and Gynecology, the Okinawa Society of Obstetrics and Gynecology, the Fukuoka City Government, and the Fukuoka City Medical Association for their valuable support.
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Miyake, Y., Tanaka, K. & Arakawa, M. ITIH3 and ITIH4 polymorphisms and depressive symptoms during pregnancy in Japan: the Kyushu Okinawa Maternal and Child Health Study. J Neural Transm 125, 1503–1509 (2018). https://doi.org/10.1007/s00702-018-1905-1
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DOI: https://doi.org/10.1007/s00702-018-1905-1