Genetic variants of the kynurenine-3-monooxygenase and postpartum depressive symptoms after cesarean section in Chinese women.
New conceptualizations of depression have emphasized the role of the kynurenine pathway (KP) in the pathogenesis of postpartum depressive symptoms (PDS). Kynurenine 3-monooxygenase (KMO) is a rate-limiting enzyme of the KP, where it catalyzes the conversion of kynurenine (KYN) to 3-hydroxykynurenine (3-HK). Previous work indicates that KMO is closely linked to the pathophysiology of depressive disorders. The purpose of this study is to investigate whether variations in the KMO gene affect PDS development after cesarean section.



A total of 710 Chinese women receiving cesarean section were enrolled in this study. PDS was determined by an Edinburgh Postnatal Depression Scale (EPDS) score ≥13. Subsequently, 24 women with PDS and 48 matched women without PDS were randomly selected for investigation of perinatal serum concentrations of KYN, 3-HK and the 3-HK/KYN ratio. The 3-HK/KYN ratio indicates the activity of KMO. In addition, 6 single nucleotide polymorphisms of the KMO gene were examined. Following this genotyping, 36 puerperant women carrying the KMO rs1053230 AG genotype and 72 matched puerperant women carrying the KMO rs1053230 GG genotype were selected for comparisons of KYN, 3-HK and 3-HK/KYN ratio levels.



The results show the incidence of PDS in the Chinese population to be 7.3%, with PDS characterized by increased serum 3-HK concentration and 3-HK/KYN ratio, versus matched postpartum women without PDS (P<0.05). Furthermore, polymorphisms of KMO rs1053230 are significantly associated with the incidence of PDS (P<0.05). The serum concentrations of 3-HK and the 3-HK/KYN ratio in postpartum women carrying the KMO rs1053230 AG genotype are significantly higher than those in matched postpartum women carrying the KMO rs1053230 GG genotype.



The presented data highlight the contribution of alterations in the KP to the pathogenesis of postpartum depression. Heightened KMO activity, including as arising from KMO rs1053230 G/A genetic variations, are indicated as one possible mechanism driving the biological underpinnings of PDS.
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China; Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang 421001, PR China; Department of Anesthesiology, Third Xiangya Hospital of Central South University, Changsha 410013, PR China.
Sai-Ying
SY
Wang
Department of Anesthesiology, Third Xiangya Hospital of Central South University, Changsha 410013, PR China.
Kai-Ming
KM
Duan
Department of Endoscopy Center, Third Xiangya Hospital of Central South University, Changsha 410013, PR China.
Xiao-Fang
XF
Tan
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China; Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang 421001, PR China.
Ji-Ye
JY
Yin
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China; Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang 421001, PR China.
Xiao-Yuan
XY
Mao
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China; Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang 421001, PR China.
Wei
W
Zheng
Department of Anesthesiology, Third Xiangya Hospital of Central South University, Changsha 410013, PR China.
Chun-Yan
CY
Wang
Department of Anesthesiology, Third Xiangya Hospital of Central South University, Changsha 410013, PR China.
Mi
M
Yang
Department of Burns and Plastic Surgery, Third Xiangya Hospital of Central South University, Changsha 410013, PR China.
Cheng
C
Peng
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China; Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang 421001, PR China.
Hong-Hao
HH
Zhou
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China; Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang 421001, PR China. Electronic address: liuzhaoqian63@126.com.
Zhao-Qian
ZQ
Liu
D000328:Adult; D044466:Asian People / Q000235:genetics / Q000523:psychology; D016022:Case-Control Studies; D002585:Cesarean Section / Q000523:psychology*; D002681:China / Q000453:epidemiology; D019052:Depression, Postpartum / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D007737:Kynurenine / Q000031:analogs & derivatives / Q000097:blood; D050601:Kynurenine 3-Monooxygenase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
C005045:3-hydroxykynurenine; D007737:Kynurenine; D050601:Kynurenine 3-Monooxygenase
Kynurenine pathway; Kynurenine-3-monooxygenase; Postpartum depressive symptoms; Single nucleotide polymorphism