rs1360780

This is a Turkish-language personalized nutrigenetics and epigenetics coaching report for individual Mehmet Efe Yildirim (Report No. 1332, dated 2023-11-21). The report analyzes the individual's genetic polymorphisms related to nutritional metabolism, food sensitivities, detoxification pathways, and other health-related traits, providing personalized dietary and lifestyle recommendations based on cited scientific literature. This is a direct-to-consumer genetic test report, not a peer-reviewed research study.

This international doctoral thesis examined gene-physical activity interactions in fibromyalgia through six studies analyzing 64 SNPs across 34 candidate genes in Spanish women. The case-control study (314 fibromyalgia cases vs. 112 controls) identified associations of rs841 (GCH1), rs1799971 (OPRM1), and rs2097903 (COMT) with fibromyalgia susceptibility (p=0.04, p=0.02, and p=0.04 respectively). Cross-sectional studies (n=274-276 fibromyalgia patients) found that SCN9A rs4453709 and other genetic polymorphisms interacted with physical activity to influence pain, fatigue, and resilience outcomes.

A candidate gene association study of 368 healthy adults examined genetic variation in FKBP5 and CRHR1 in relation to cortisol response to acute psychosocial stress (Trier Social Stress Test). rs4713902 in FKBP5 showed the strongest association with baseline cortisol (p=0.0004, dominant model). Three CRHR1 SNPs (rs7209436, rs110402, rs242924) were associated with peak cortisol response (p=0.0029-0.0047, recessive models). Sex-specific effects and interactions with trait anxiety were observed.

Cross-sectional study of 411 Italian male prisoners examining gene-environment interactions between FKBP5 haplotypes (rs3800373, rs9296158, rs1360780, rs9470080) and childhood trauma in predicting aggressive behavior. FKBP5 H2/H2 diplotype showed significant association with lifetime aggression (BGHA, P=.012) and violent behavior in jail (P=.025) only in individuals exposed to childhood trauma, particularly physical abuse. No main effect of FKBP5 was observed; the interaction was significant (P=.004; P=.01 after FDR correction). H1 haplotype carriers had increased risk of substance dependence (OR 1.8, 95% CI 1.16-2.70).

This genetic association study examined whether rs1049353 (CNR1 endocannabinoid receptor gene) moderates the effect of childhood physical abuse on anhedonia and depression. In the primary sample of 1,041 young adult women, carriers of the minor A allele showed attenuation of the abuse-anhedonia relationship (57% of GG individuals with abuse reported anhedonia vs. only 29% of AA/AG carriers; interaction OR=0.31, p=0.014). These findings were replicated in an independent sample of 1,934 Australian heroin-dependent individuals and controls (interaction OR=0.79, p=0.02). The protective effect of the rs1049353 A allele on major depressive disorder was largely attributable to its effect on anhedonic depression.

Study of 211 participants (primarily African American, low-income) investigated interactions of FKBP5 SNP rs9296158 with PTSD symptoms on glucocorticoid receptor sensitivity and gene expression. Risk allele A carriers showed increased GR sensitivity (cortisol suppression P=.03) and altered gene expression patterns in PTSD. FKBP5 SNP×PTSD symptom interaction significantly predicted expression of 41 transcripts (including FKBP5 and IL18R1), with replication in 98 independent samples, suggesting FKBP5 polymorphisms define distinct PTSD endocrine subtypes.

This systematic review of 98 studies examined biological predictors of clozapine response in treatment-resistant schizophrenia patients. Of 379 different gene variants investigated across 70 genetic studies, only three variants (DRD3 Ser9Gly rs6280, HTR2A His452Tyr, and GNB3 C825T) achieved independent replication. Non-genetic predictors included higher prefrontal cortical volumes and lower HVA:5-HIAA ratio in cerebrospinal fluid.

This study examined whether two FKBP5 polymorphisms (rs1360780 and rs3800373) predict antidepressant treatment response in 246 geriatric depression patients treated with paroxetine or mirtazapine in a double-blind randomized trial. Unlike previous reports, the authors found no significant associations between FKBP5 variants and treatment outcomes by HDRS-17 scores or time to remission, with only marginal non-significant findings on HDRS-21 measures that were opposite in direction to prior studies. The results suggest FKBP5 genetic variation may not play a major role in antidepressant response in elderly patients.

A systematic review of 98 studies investigating biological predictors of clozapine response in treatment-resistant schizophrenia. Of 70 genetic studies examining 379 variants, only three genetic variants have independently replicated findings: DRD3 Ser9Gly (rs6280), HTR2A His452Tyr, and GNB3 C825T (rs5442/rs5443). Non-genetic predictors include higher prefrontal cortical structural integrity and activity, and lower HVA:5-HIAA ratio in cerebrospinal fluid.

This study examined gene-environment (G×E) interactions between HPA axis variants (CRHR1, NR3C1, FKBP5) and childhood trauma on anxiety sensitivity in South African adolescents (n=951). Significant associations and interactions were found in gender- and ethnicity-specific analyses, including FKBP5 rs9296158 (p=0.025) and rs737054 (p=0.045) in Coloured males, and protective effects of NR3C1 rs190488 (p=0.009) and rs10482605 (p=0.036) with increasing trauma in Xhosa participants.

This cross-sectional study of 762 African American adults found that four FKBP5 SNPs (rs9296158, rs3800373, rs1360780, rs9470080; minimum P=0.0004) significantly interacted with severity of childhood abuse to predict adult PTSD symptoms, independent of non-child abuse trauma exposure, depression severity, age, sex, and genetic ancestry. The SNPs showed no main effects on PTSD or interactions with non-child abuse trauma, suggesting a specific gene-by-childhood-environment interaction mechanism.

This review examines pharmacogenetic findings from the STAR*D trial, a large-scale antidepressant treatment outcome study involving 1953 participants. Key findings include associations of rs1954787 (GRIK4) and rs7997012 (HTR2A) with better treatment response, rs1360780 (FKBP5) with rapid antidepressant response, and rs2818224 (GRIK2, OR ~8) and rs4825476 (GRIA3, OR 1.9) with treatment-emergent suicidal ideation.

This doctoral thesis conducted multiple candidate gene association studies in 274-426 southern Spanish women with fibromyalgia to investigate gene-physical activity/sedentary behavior interactions with pain, fatigue, and resilience. Study III identified rs841 (GCH1) GG genotype (OR=0.61, p=0.04) and rs2097903 (COMT) AT/TT genotypes (OR=1.66, p=0.04) associated with fibromyalgia susceptibility, and confirmed rs1799971 (OPRM1) GG genotype (OR=0.58, p=0.02) confers genetic risk. Study IV found rs6311/rs6313 (HTR2A) polymorphisms individually associated with algometer pain score, and gene-sedentary behavior interactions involving rs4680/rs165599 (COMT), rs1383914 (ADRA1A), rs12994338/rs4453709 (SCN9A), and rs6860 (CHMP1A) significantly associated with pain outcomes. SCN9A emerged as most robust gene for fibromyalgia phenotype.