rs1042714

This systematic review analyzed genetic associations with gastroschisis from 1980-2017, identifying 14 SNPs from 10 genes associated with crude risk and 30 SNPs from 14 genes with stratified risk. Four SNPs showed significant associations: rs4961 (ADD1, p=0.023), rs5443 (GNB3, p=0.002), rs1042713 (ADRB2, p=0.007), and rs1042714 (ADRB2, p=0.006). The findings suggest genetic susceptibility in gastroschisis is not restricted to gene-environment interactions, with blood pressure regulation genes playing a significant role in vascular disruption pathogenesis.

Case-control study of 216 cervical vertigo patients and 204 controls identifying SNPs in ADRA1A, ADRB1, ADRB2, and NPY genes significantly associated with cervical vertigo risk (ORs 0.62-2.07) and clinical prognosis markers (JOA score and recovery rate). ADRA1A rs3802241 showed OR=2.07 for disease risk and protective effect on prognosis; NPY variants predicted recovery outcomes.

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.

This genetic association study identified ADRB2 SNP rs2400707 as protective against PTSD symptoms in the context of childhood adversity (β=0.243, P=1.02×10^-5 in discovery cohort; P=0.0009 in replication cohort). The AA homozygotes showed lower PTSD severity with ≥2 categories of adverse childhood experiences across two independent cohorts (n=810 soldiers and n=2,083 civilians), with combined interaction effect P=3.97×10^-7. The protective A allele tags the H1 haplotype, hypothesized to represent low-transcription ADRB2 variant.

This comprehensive review examines the genetic background of nonalcoholic fatty liver disease (NAFLD), focusing on variants identified by genome-wide association studies (GWAS) and candidate gene studies. The most significant GWAS-identified variants are PNPLA3 rs738409 (I148M), which strongly associates with increased liver steatosis, fibrosis severity, and HCC risk (12-fold increased risk for homozygous carriers), and TM6SF2 rs58542926 (E167K), which increases NASH progression but reduces cardiovascular risk. The review also discusses numerous candidate genes involved in lipid and glucose metabolism and liver injury mechanisms.

This candidate gene association study examined 14 SNPs in ADRB2 and COMT genes in 1,004 Western Australian adolescents (age 17) to identify genetic variants associated with chronic musculoskeletal complaints. Of the SNPs tested, only rs2053044 in ADRB2 (recessive model) showed association with chronic disabling neck and low back pain (OR = 2.49; 95% CI = 1.25-4.98; p = 0.01) and pain in 3-4 body areas (OR = 1.86; 95% CI = 1.13-3.06; p = 0.02). The findings suggest that genetic variants in ADRB2 may be involved in regulating chronic musculoskeletal pain in adolescents.

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 large case-control study of 7,808 Danish white subjects examined the association of two ADRB2 gene variants (Arg16Gly and Gln27Glu) with obesity, hypertension, and type 2 diabetes. The study found no consistent evidence for association with obesity or hypertension in case-control analyses; however, nominal associations with systolic blood pressure were observed (Gly allele and Glu allele showing effects in women). A weak association of the Arg16 allele with type 2 diabetes was found (p=0.03), and the Arg/Gly genotype was associated with metabolic syndrome (p=0.003). Overall, neither variant appeared to be a major contributor to these metabolic diseases.

Study of 202 female subjects examining ADRB2 haplotypes defined by 8 SNPs and their associations with psychological traits, resting blood pressure, and temporomandibular disorder (TMD) risk. Three major haplotypes (H1, H2, H3) were identified representing 97.4% of variants. Heterozygotes carrying one H1 haplotype showed protective effects: highest positive psychological traits, higher resting blood pressure, and ~10-fold lower TMD risk (1.3% incidence vs 20% in H2/H2 homozygotes; RR=8.0-11.3 for homozygotes vs heterozygotes).

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.