rs1799983

This is a comprehensive review of gene-environment interactions in hypertension, summarizing recent research on how genetic variants interact with lifestyle factors (diet, alcohol, smoking, obesity, physical activity) to influence blood pressure regulation. The paper discusses key genetic variants including GNB3-C825T, BCL11B-rs8022678, NOS3-rs1799983, CYP4A11 variants, and FTO-rs9930333, and recommends lifestyle modifications and selective genetic testing for hypertension management in community healthcare settings.

This case-control study of 69 acute mountain sickness (AMS) patients and 95 matched acclimated Han Chinese individuals investigated five SNPs in hypoxia-related genes. The HSPA1A rs1008438 polymorphism showed a significant association with AMS susceptibility (OR = 0.36, 95% CI: 0.14–0.92 in the additive model), suggesting it may be a Han-specific genetic risk factor for AMS development.

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.

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 candidate gene study of 130 Danish children with type 1 diabetes examined associations between 20 diabetes-related SNPs and diabetic retinopathy progression over 16 years. The CTSH/rs3825932 variant was associated with reduced risk of progression to proliferative diabetic retinopathy (OR=0.20, p=2.4×10⁻³, p_adjust=0.048), while ERBB3/rs2292239 was associated with increased risk of two-step DR progression (OR=2.76, p=7.5×10⁻³, p_adjust=0.15). The CTSH association remained significant after multiple testing correction.

Genetic polymorphisms in oxidative stress-related genes were associated with treatment outcomes in aggressive B-cell non-Hodgkin lymphoma. In discovery (n=337) and validation (n=572) cohorts, rare homozygotes for MPO rs2243828 (HR=1.87, P=0.013) and AKR1C3 rs10508293 (HR=2.09, P=0.0032) were associated with increased risk of progression, while NCF4 rs1883112 rare homozygotes showed protective effects against progression (HR=0.66, P=0.06 discovery; HR=0.66, P=0.05 validation). Meta-analysis confirmed NCF4 association with improved survival outcomes (HR=0.66, P<0.01).

A hospital-based case-control study in rural and urban India (1,204 cases; 1,212 controls) examined genetic and lifestyle risk factors for breast cancer. Four SNPs in FGFR2 (rs1219648, rs2420946, rs2981575, rs2981582) showed positive associations with breast cancer (ORs 1.32-1.47). Additional SNPs in obesity and metabolic genes (rs374748 in FBN2, rs2922763 in HNF4G, rs2116830 in KCNMA1, rs11121832 in MTHFR, rs16886165 in MAP3K1, rs11594610 in TCF7L2, rs2274459 in MLN) were associated with increased breast cancer risk. Waist-to-hip ratio ≥0.95 showed strong association (OR 3.78; 95% CI 2.92-4.89), and women living first 20 years in rural areas showed protective effect (OR 0.77).

Genetic association study of nitric oxide synthase genes (NOS1, NOS2, NOS3) in neural tube defects (NTDs) in 3109 Caucasian samples from 745 families. The most significant association was rs4795067 (NOS2, AG genotype) with cranial NTDs (genoPDT p=0.0014), and a significant interaction between rs9658490 (NOS1, G allele) and MTHFR C677T polymorphism with anencephaly/acrania (p=0.0014). Results implicate all three NOS genes in NTD risk both independently and through interactions with MTHFR.

This case-control study investigated associations between five NOS3 gene polymorphisms and osteonecrosis of the femoral head (ONFH) in Korean patients with systemic lupus erythematosus. Two exonic NOS3 variants were significantly associated with ONFH risk: rs1549758 (Asp258Asp) and rs1799983 (Glu298Asp, G894T) showed OR 2.7-3.8 (p=1.0×10⁻⁵-5.0×10⁻⁴). The rs1799983-rs1800780 haplotype G-A was protective (OR 0.39, p=1.6×10⁻³), while haplotype T-A increased risk (OR 3.17-3.73, p=2.0×10⁻⁵-6.0×10⁻⁴).

Candidate gene association study of 67 genetic variants in 27 inflammation and DNA repair genes with hepatitis A virus (HAV) infection susceptibility in 6,779 NHANES III participants (2,619 non-Hispanic whites, 2,095 non-Hispanic blacks, 2,065 Mexican Americans). Among Mexican Americans, ABCB1 rs1045642 T allele was associated with lower HAV seropositivity risk (OR=0.79, p<0.001), while TGFB1 rs1800469 and XRCC1 rs1799782 T alleles were associated with increased risk (OR=1.38 and 1.57, respectively). CAT rs769214 and CYP2E1 rs2031920 showed marginal associations with decreased and increased HAV risk, respectively.

Population-based case-control study of 389 infants with congenital limb deficiencies and 980 controls examining 132 SNPs in 20 candidate genes involved in limb development, angiogenesis, and coagulation. Among non-Hispanic white infants, SNPs in FGF10 (rs10805683: OR=1.99, 95% CI=1.43-2.77; rs13170645: OR=2.37, 95% CI=1.48-3.78) showed significant associations with limb deficiencies after multiple testing correction, with supportive evidence for genes including EN1, WNT7A, CYP26B1, SHH, and TBX5.

A case-control study of 326 cases and 748 controls identified 25 SNPs in genes involved in platelet activation, angiogenesis, and inflammatory response that modify the risk of aspirin-related upper gastrointestinal hemorrhage (UGIH). Seven SNPs (rs1387180, rs2238631, rs1799964, rs5050, rs689466, rs1799983, rs7756935) were positive modifiers increasing UGIH risk in aspirin users (RERI 1.75-4.95), while nine SNPs (rs2243086, rs1131882, rs4311994, rs10120688, rs4251961, rs3778355, rs1330344, rs5275, rs3779647) were negative modifiers reducing risk (RERI -2.74 to -0.95). Aspirin exposure alone increased UGIH risk approximately 5.82-fold (95% CI: 2.2-10.08).

Case-control association study examining NOS3 polymorphisms and psoriasis risk in 368 patients and 400 controls. The -786 C allele (rs2070744) was significantly more frequent in patients (72% vs 59%, OR 1.70, 95% CI 1.24-2.33, p<0.001), and the intron 4 VNTR 4-repeat allele was also more frequent (32% vs 21%, OR 1.78, p<0.001). The Glu298Asp polymorphism (rs1799983) showed no significant association with psoriasis risk. None of the NOS3 variants were associated with hypertension or ischemic cardiac disease in this population.

This comprehensive review examines genetic association studies on prostate cancer, discussing GWASs that have identified over 75 variants associated with PCa risk (as of February 2016), with major susceptibility regions at 8q24, 17q12, 17q24, 10q11, and 19q13. The paper also reviews candidate gene-based approaches targeting genes involved in androgen signaling, carcinogen metabolism, DNA repair, vitamin D signaling, inflammation, angiogenesis, and cellular adhesion, as well as regulatory RNA genes.

The NOS3 -786 T/C polymorphism (rs2070744) is associated with elite performance in power-oriented sports (throwing, jumping, sprinting) in Spanish athletes. The T allele was significantly more frequent in power athletes (71%) compared to endurance athletes (55%, P=0.003) and controls (56%, P=0.015). TT genotype was overrepresented in power athletes (57%) versus endurance athletes (33%, P=0.017) and controls (34%, P=0.026). No association was found with elite endurance performance.

This is a literature review examining the role of genetic factors in diabetic nephropathy (kidney disease) in type 2 diabetes mellitus. The review highlights candidate genes in the renin-angiotensin system (ACE and AGT) and endothelial factors (eNOS3 and EDN1). Meta-analysis revealed associations of three eNOS3 polymorphisms (4b/a, T-786C, G984T) with diabetic nephropathy (OR=1.12-1.77 and 1.11-1.50); the ACE I/D polymorphism showed association particularly in Asian populations (D-allele OR=1.32, DD genotype OR=1.67); M235T in AGT showed inconsistent associations across populations.

A systematic review and meta-analysis of 9 case-control studies (1917 CHD cases, 1863 controls, 1718 maternal cases, 1666 maternal controls) examining MTHFD1 G1958A (rs2236225) polymorphism association with congenital heart disease (CHD). The fetal meta-analysis found no significant overall association, but subgroup analysis showed the AA genotype increased Tetralogy of Fallot (TOF) risk (OR=2.82-3.09). Maternal analysis revealed the GA genotype increased CHD risk (OR=1.22-1.17). Racial differences were observed, with Caucasians showing increased risk.

This dissertation investigated the genetic basis of violent criminal behavior, antisocial personality disorder (ASPD), and broader antisocial behavior through GWAS and meta-analyses in Finnish and international populations. Study I identified an intronic CDH13 variant (rs11649622, OR=2.7, p=4.19×10⁻⁶) associated with extremely violent offending, replicated in homicide offenders (p=5.3×10⁻⁷, OR=2.17). Study II revealed the first genome-wide significant association between LINC00951 variant rs4714329 (OR=1.59, p=1.6×10⁻⁹) and ASPD. Study III meta-analysis of 16,400 individuals found no genome-wide significant associations with broader antisocial behavior, though polygenic risk scores explained ~5% of phenotypic variance.

This family-based case-control study examined 50 SNPs across three nitric oxide synthase genes (NOS1, NOS2A, NOS3) in 1,065 Parkinson disease cases and 1,180 controls from 695 families. Significant associations with PD were found for 8 NOS1 SNPs (rs3782218, rs11068447, rs7295972, rs2293052, rs12829185, rs1047735, rs3741475, rs2682826; p=0.00083-0.046) and 7 NOS2A SNPs (rs2072324, rs944725, rs12944039, rs2248814, rs2297516, rs1060826, rs2255929; p=0.0000040-0.047) in early-onset sporadic PD families. Gene-environment interactions were detected between NOS1 SNPs (rs12829185, rs1047735, rs2682826) and pesticide exposure (p=0.012-0.034) and between NOS2A SNPs (rs2248814, rs1060826) and cigarette smoking (p=0.013-0.021).

This is a study design and baseline characteristics paper for a nested case-control pharmacogenetic study of antihypertensive drug treatment. The study recruited 5,126 participants (794 myocardial infarction cases, 4,997 controls) through Dutch community pharmacies to assess whether specific genetic polymorphisms in renin-angiotensin system genes (AGT, ACE, AGTR1), alpha-adducin (ADD1), and other cardiovascular-related genes (GNB3, NOS3) modify the effect of antihypertensive drugs on myocardial infarction risk. The paper presents recruitment methodology, participant baseline characteristics, and selected genetic polymorphisms for analysis rather than association results.

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.