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Influence of genetic polymorphisms in homocysteine and lipid metabolism systems on antidepressant drug response.

ABSTRACT: BACKGROUND:Variation in genes implicated in homocysteine and lipid metabolism systems may influence antidepressant response for patients with major depressive disorder (MDD). This study aimed to investigate whether association of polymorphisms on the MTHFR, ApoE and ApoA4 genes with the treatment response in MDD subjects. METHODS:A total of 281 Han Chinese MDD patients received a single antidepressant drug (SSRI or SNRI) for at least 6?weeks, among whom 275 were followed up for 8?weeks. Their response to 6?weeks' treatment and remission to 8?weeks' treatment with antidepressant drugs was determined by changes in the 17-item Hamilton Depression Rating Scale (HARS-17) score. Single SNP and haplotype associations with treatment response were analyzed by UNPHASED 3.0.13. Logistic regression analysis was used to explore the interactions between genotypes and gender or drug type on treatment outcome, only those SNPs that had interactional association with gender or drug type were subjected to further stratified analysis. RESULTS:In total group, the haplotype (C-A) in MTHFR (rsl801133 and rs1801131) and the ApoE rs405509 AA genotype were significantly associated with better efficacy of antidepressants; In gender subgroups, only haplotype (C-A) in MTHFR (rsl801133 and rs1801131) was significantly associated with better efficacy of antidepressants in male subgroup; In drug type subgroup, the haplotype (C-A) in MTHFR (rsl801133 and rs1801131) and haplotype (G-C) in ApoE (rs7412 and rs405509) were associated with better efficacy of antidepressants in SNRI treated subgroup; The ApoA4 rs5092 G allele and GG genotype were associated with worse efficacy of antidepressants in SNRI treated subgroup. CONCLUSIONS:Genetic polymorphisms in homocysteine and lipid metabolism systems are associated with antidepressant response, particularly for the interactions of the certain genetic with gender or drug type.

SUBMITTER: Yuan B

PROVIDER: S-EPMC7427977 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Influence of genetic polymorphisms in homocysteine and lipid metabolism systems on antidepressant drug response.

Yuan Baoyu B Sun Xiaoyan X Xu Zhi Z Pu Mengjia M Yuan Yonggui Y Zhang Zhijun Z

BMC psychiatry 20200814 1

<h4>Background</h4>Variation in genes implicated in homocysteine and lipid metabolism systems may influence antidepressant response for patients with major depressive disorder (MDD). This study aimed to investigate whether association of polymorphisms on the MTHFR, ApoE and ApoA4 genes with the treatment response in MDD subjects.<h4>Methods</h4>A total of 281 Han Chinese MDD patients received a single antidepressant drug (SSRI or SNRI) for at least 6 weeks, among whom 275 were followed up for 8 ...[more]

PMID: 32795354

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Project description:Aims: To investigate the effects of single nucleotide polymorphisms (SNPs) in genes of one-carbon metabolism (OCM) related enzymes and anti-epileptic drug (AED) monotherapy on homocysteine (Hcy) metabolism in patients with epilepsy, and to further explore specific SNPs that may increase patients' susceptibility to the effects of AEDs on the Hcy imbalance. Method: This case-control study analyzed 279 patients with epilepsy, including patients receiving monotherapy with valproate (VPA) (n = 53), oxcarbazepine (OXC) (n = 71), lamotrigine (LTG) (n = 55), or levetiracetam (LEV) (n = 35) and patients who had not taken any AEDs (controls, n = 65) for at least 6 months. Serum levels of vitamin B12 (vit B12), folate (FA) and Hcy were measured, and 23 SNPs in 13 genes of OCM-related enzymes were genotyped in all patients. Results: Methylenetetrahydrofolate reductase (MTHFR) rs1801133 was associated with elevated serum Hcy levels in patients with epilepsy (P < 0.001), and patients presenting the TT genotype exhibited higher serum Hcy levels than patients with the CC (P < 0.001) or CT (P < 0.001) genotype. A subsequent multiple linear regression analysis showed that AED monotherapy with VPA (vs. control: P = 0.023) or OXC (vs. control: P = 0.041), and genotypes of MTHFR rs1801133 TT (vs. CC: P < 0.001; vs. CT: P < 0.001), transcobalamin 2 (TCN2) rs1801198 CC (vs. GC: P = 0.039) and folate receptor 1 (FOLR1) rs2071010 AA (vs. GA: P = 0.031) were independent risk factors for higher Hcy levels. In the subgroup analysis of patients taking OXC, we found that patients with genotypes of MTHFR rs1801133 TT (vs. CC: P = 0.001; vs. CT: P < 0.001) and TCN2 rs1801198 CC (vs. GC: P = 0.021; vs. GG: P = 0.018) exhibited higher serum Hcy levels. Conclusions: VPA, OXC, and genotypes of MTHFR rs1801133 TT, TCN2 rs1801198 CC, and FOLR1 rs2071010 AA are all independent risk factors for elevated Hcy levels in patients with epilepsy. Moreover, genotypes of MTHFR rs1801133 TT and TCN2 rs1801198 CC may increase patients' susceptibility to the effect of OXC on disrupting Hcy homeostasis.

Project description:BACKGROUND: Information about the interactions of single nucleotide polymorphisms (SNPs) and overweight/obesity on serum lipid profiles is still scarce. The present study was undertaken to detect ten SNPs and their interactions with overweight/obesity on serum lipid levels. METHODS: A total of 978 normal weight and 751 overweight/obese subjects of Bai Ku Yao were randomly selected from our previous stratified randomized cluster samples. Normal weight, overweight and obesity were defined as a body mass index (BMI) < 24, 24-28, and > 28 kg/m(2); respectively. Serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) A1 and ApoB levels were measured. Genotyping of ATP-binding cassette transporter A1 (ABCA-1) V825I, acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) rs1044925, low density lipoprotein receptor (LDL-R) AvaII, hepatic lipase gene (LIPC) -250G>A, endothelial lipase gene (LIPG) 584C>T, methylenetetrahydrofolate reductase (MTHFR) 677C>T, the E3 ubiquitin ligase myosin regulatory light chain-interacting protein (MYLIP) rs3757354, proprotein convertase subtilisin-like kexin type 9 (PCSK9) E670G, peroxisome proliferator-activated receptor delta (PPARD) +294T>C, and Scavenger receptor class B type 1 (SCARB1) rs5888 was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. The interactions were detected by factorial design covariance analysis. RESULTS: The genotypic and allelic frequencies of LIPC and PCSK9 were different between normal weight and overweight/obese subjects, the genotypic frequency of LIPG and allelic frequency of MYLIP were also different between normal weight and overweight/obese subjects (P < 0.05-0.001). The levels of TC, ApoA1 (ABCA-1); TC, LDL-C, ApoA1, ApoB and ApoA1/ApoB (LIPC); TG, HDL-C, and ApoA1 (LIPG); TC, HDL-C, LDL-C, ApoA1 and ApoB (MTHFR); HDL-C and ApoA1 (MYLIP) in normal weight subjects were different among the genotypes (P < 0.01-0.001). The levels of LDL-C, ApoB and ApoA1/ApoB (ABCA-1); HDL-C, ApoA1, ApoB and ApoA1/ApoB (LIPC); TC, HDL-C, ApoA1 and ApoB (LIPG); TC, TG, HDL-C, LDL-C, ApoA1 and ApoB (MTHFR); TC, TG and ApoB (MYLIP); TG (PCSK9); TG, ApoA1 and ApoB (PPARD); and TC, HDL-C, LDL-C, ApoA1 and ApoB (SCARB1) in overweight/obese subjects were different among the genotypes (P < 0.01-0.001). The SNPs of ABCA-1 (LDL-C and ApoA1/ApoB); LIPC (TC, LDL-C, ApoA1 and ApoB); LIPG (ApoB); MTHFR (TC, TG and LDL-C); MYLIP (TC and TG); PCSK9 (TG, HDL-C, ApoB and ApoA1/ApoB); PPARD (TG and ApoA1/ApoB); and SCARB1 (TG, ApoA1 and ApoB) interacted with overweight/obesity to influence serum lipid levels (P < 0.05-0.001). CONCLUSIONS: The differences in serum lipid levels between normal weight and overweight/obese subjects might partly result from different genetic polymorphisms and the interactions between several SNPs and overweight/obesity.

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Influence of genetic polymorphisms in homocysteine and lipid metabolism systems on antidepressant drug response.

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Influence of genetic polymorphisms in homocysteine and lipid metabolism systems on antidepressant drug response.

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