rs4994

This study investigates the association of the ADRB3 rs4994 (Trp64Arg) polymorphism with serum urate and gout across New Zealand European, Māori, and Polynesian populations. The Arg64 allele was significantly associated with increased serum urate in Western Polynesian subjects (β = 0.036, P = 0.004), but showed inconsistent associations with gout risk across different population groups, with no significant overall association when meta-analyzed.

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 two-part genetic association study in Korean populations examining SNP associations with serum uric acid (SUA) concentration. Study 1 compared minor allele frequencies of 40 SNPs associated with SUA across Korean, Japanese, and European descent populations in 1,957 subjects. Study 2 analyzed associations in 402 RA patients, finding rs12734001 (PPP1R12B) most significantly associated with SUA levels (P_trend = 2.29 × 10^-9) and rs3741414 (INHBC) with P_trend = 0.01. Results showed Korean SNP frequencies were more similar to Japanese than European populations.

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.

A comprehensive review of nutrigenetics and nutrigenomics examining how genetic variants influence individual responses to nutrients and dietary interventions. The paper discusses associations between numerous SNPs (rs9939609 in FTO, rs2287019 in GIPR, rs7903146 in TCF7L2, rs5219 in KCNJ11, and many others) and metabolic traits including obesity, type 2 diabetes, and other chronic diseases, along with epigenetic mechanisms by which phytochemicals (curcumin, resveratrol, lycopene) modulate gene expression. The review synthesizes current evidence for precision nutrition approaches tailored to individual genetic profiles.

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.

Case-control study examining adrenergic receptor gene polymorphisms in fibromyalgia patients from Mexican and Spanish populations. The beta(2)-AR AC haplotype was a significant risk factor (42.1% in Mexican patients vs 30.5% controls, p=0.04; 50.4% Spanish patients vs 40.0% controls, p=0.05). The rs574584 GG genotype in Mexican patients associated with higher disability scores, morning stiffness, and fatigue.

This pharmacogenetic study of 210 subjects from the Personalized Medicine Research Project examined whether polymorphisms in β-adrenergic receptor genes and CYP2D6 are associated with intraocular pressure (IOP) response to topical β-blockers. A coding SNP in ADRB2 (rs1042714, Gln27Glu) was significantly associated with increased IOP response (≥20% reduction) with an odds ratio of 2.00 (95% CI, 1.00-4.02; P=.05). CYP2D6 phenotypes and optineurin/myocillin polymorphisms were not significantly associated with IOP response.

This prospective study of 16,143 individuals from the Malmö Preventive Project (mean follow-up 23 years) investigated whether genetic variants in 26 genes previously associated with type 2 diabetes or metabolic syndrome components could predict future development of metabolic syndrome. Polymorphisms in TCF7L2 (rs7903146, OR 1.10, p=0.00097), FTO (rs9939609, OR 1.08, p=0.0065), WFS1 (rs10010131, OR 1.07, p=0.0078), and IGF2BP2 (rs4402960, OR 1.07, p=0.021) predicted metabolic syndrome development, with TCF7L2, WFS1, and IGF2BP2 acting through hyperglycemia and FTO through obesity. A composite genotype score of 17 polymorphisms predicted metabolic syndrome risk (OR 1.04, p<0.00001), with carriers of ≥19 risk alleles having 51% increased risk compared to carriers of ≤12 alleles.

This case-control study of 1,881 Scandinavian women (649 with gestational diabetes mellitus, 1,232 controls) found that the TCF7L2 rs7903146 variant confers increased risk of gestational diabetes mellitus, with heterozygotes showing OR=1.56 (95% CI 1.26-1.93, p=3.7×10⁻⁵) and homozygotes OR=2.05 (95% CI 1.41-2.99, p=0.0001). Four other polymorphisms previously associated with type 2 diabetes (ADIPOQ rs1501299, PPARG rs1801282, PPARGC1A rs8192678, FOXC2 -512C>T, ADRB3 rs4994) were not significantly associated with gestational diabetes mellitus in this population.

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.