rs1801133

This study examined genetic and epigenetic markers associated with chemotherapy-induced oral mucositis in 87 pediatric patients with hematological neoplasms, with 81.9% developing mucositis. Global DNA methylation was significantly reduced in children who recovered from mucositis (18% vs 40% in healthy controls, p<0.05), and the DNMT1 rs2228611 SNP showed association with global methylation levels in cancer patients with mucositis history. miR-9-1 and miR-9-3 methylation patterns were associated with tumor status rather than mucositis.

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 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.

A case-control study of 152 NTD patients and 169 controls in Han Chinese population identified three folate metabolism pathway SNPs associated with neural tube defects: rs2236225 in MTHFD1 (allele A, OR=1.500; AA genotype OR=2.862), rs1801133 in MTHFR (allele T, OR=1.552; TT genotype OR=2.344), and rs1801394 in MTRR (allele G, OR=1.533; GG genotype OR=2.355). The study demonstrates genetic variation in folate metabolism significantly affects NTD susceptibility.

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 Brazilian epidemiological study describes clinical, demographic, and environmental features of 188 nonsyndromic cleft lip and/or palate (NSCL/P) patients. Cleft lip and palate was most common (55.8%), with male predominance (64.4%). Systemic alterations were found in 23.4% of patients, primarily otorhinolaryngological and respiratory issues. Over 80% of mothers reported no vitamin supplementation during early pregnancy, highlighting a key modifiable risk factor for NSCL/P prevention.

This study investigated how genetic polymorphisms in FPGS (rs1544105), GGH (rs3758149), and MTHFR (rs1801133) affect serum methotrexate levels and metabolism in 91 Chinese children with acute lymphoblastic leukemia. The GGH rs3758149 CC genotype was associated with significantly lower MTX C/D ratios at 24 hours (12.09 vs 16.80 µmol/l per g/m², P < 0.05) in female patients, and the A-T-T haplotype was associated with higher MTX levels above therapeutic threshold (47.4% vs 19.4%, P = 0.01). The findings identify a novel gender-specific pharmacogenetic effect not previously documented in MTX metabolism.

A candidate gene association study screening 1,421 SNPs in 407 cancer-related genes identified two novel susceptibility loci for childhood B-precursor acute lymphoblastic leukemia: rs6966 in PPP1R13L/ERCC2 region (OR=3.74, 95% CI 2.31-6.04, p=4.55×10⁻⁹) and rs414580 in MSR1 (OR=3.93, 95% CI 2.31-6.69, p=6.09×10⁻⁸). A third SNP, rs11762213 in MET, showed borderline significance (p=2.97×10⁻²).

Case-control study of 501 young stroke patients and 1,211 controls examining 58 polymorphisms in 17 genes involved in methionine metabolism. Multiple logistic regression identified four independent risk factors for early-onset ischaemic stroke: rs10037045 BHMT (OR 1.38, p=0.033), rs682985 BHMT2 (OR 1.46, p=0.017), rs1051319 CBS (OR 3.75, p<0.0001), and rs202680 FOLH1 (OR 3.00, p<0.0001). Haplotype analyses identified significant associations with BHMT, CBS, FOLH1, MTR, PON2, TCN2 and TYMS haplotypes and stroke risk.

A case-control study of 576 fetuses/newborns with neural tube defects (NTDs) and 594 controls in a Chinese population examined MTHFR and COMT gene variants. The MTHFR rs1801133 TT genotype was associated with increased NTD risk (OR=1.37), and a synergistic interaction between COMT rs737865 CC and MTHFR rs1801133 TT genotypes showed over 3-fold increased risk for NTDs (OR=3.02) and anencephaly (OR=3.39), suggesting these variants interact to modulate folate metabolism and increase birth defect susceptibility.

This cohort study examined the association between the MTHFR C677T polymorphism (rs1801133) and cardiovascular disease outcomes in 13,748 Danish adults without mandatory folic acid fortification. Individuals with the MTHFR TT genotype had a higher risk of ischemic heart disease (IHD) (HR 1.38, 95% CI 1.11–1.71, p=0.004), but no associations were found with hypertension, dyslipidemia, stroke, or all-cause mortality. The association with IHD was not modified by serum folate or B12 status.

This literature review examines the influence of genetic polymorphisms on obesity development and adaptive responses to physical activity, focusing on five candidate genes: COMT (rs4680, Val158Met), DRD2 (rs1800497 Taq1A and rs1799732), FABP2 (rs1799883, Ala54Thr), FTO (rs9939609, A/T), and UCP1 (rs1800592, A-3826G). The review synthesizes molecular mechanisms, phenotypic associations, and implications for human health and training adaptations, noting that physical activity reduces the FTO genetic effect on obesity risk by 30-80% and that various polymorphisms show differential impacts on body composition and metabolic responses to exercise.

Population distribution study of MTHFR C677T (rs1801133) and A1298C (rs1801131) variants in Israeli subpopulations. Ashkenazi Jews showed 1.87-fold higher frequency of 677T allele and 1.81-fold lower frequency of 1298C allele compared to non-Ashkenazi Jews. These polymorphisms are associated with reduced MTHFR enzyme activity and methotrexate toxicity risk, with implications for personalized medicine and drug dosing.

This meta-analysis of 106 studies (100 articles, 625 total retrieved) evaluates associations between MTHFR gene polymorphisms (C677T rs1801133 and A1298C rs1801131) and colorectal cancer (CRC) risk across 37 Asian, 50 Caucasian, 6 Indian, 4 African, and 7 mixed-race populations. MTHFR C677T polymorphism reduces CRC risk in Asian and mixed-race populations but increases risk in Indians. MTHFR A1298C polymorphism may play a protective role in CRC development, with several genetic models showing reduced susceptibility (e.g., CC vs AA: OR=0.729, 95% CI=0.582-0.913; C vs A: OR=0.905, 95% CI=0.833-0.984).

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).

This study examined PAH-related DNA adduct levels in 111 female never-smokers from Iran, evaluating 21 SNPs in 14 xenobiotic metabolism genes and 12 SNPs in 8 DNA repair genes. DNA adduct levels were significantly lower with NAT2 slow alleles (β=-0.24, p=0.01) and ERCC5 non-risk genotype (β=0.16, p=0.04), but higher with MPO risk alleles (β=0.21, p=0.01). The combination of phase I genes and measured NER capacity explained 17% more variation in adduct levels than environmental exposure alone (r²=0.24 vs 0.07), demonstrating the importance of genetic polymorphisms in PAH metabolism and DNA repair capacity.

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.

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.

Meta-analysis of 83 case-control studies (35,758 individuals) examining associations between homocysteine levels, folate, vitamin B12, and MTHFR polymorphisms with cancer risk. High homocysteine levels showed strong association with overall cancer risk (OR 5.06, 95% CI 4.59-5.52), while low folate was protective (OR -2.68). MTHFR C677T TT/CC genotype showed significant association with cancer risk (OR 1.18, 95% CI 1.05-1.33).

A candidate gene association study in 100 Russian vitiligo patients and 100 controls identified a strong novel association between GSTP1 rs1138272 (Ala114Val, OR=13.03, Bonferroni-adjusted P=0.0015) and vitiligo susceptibility. Cumulative analysis of multiple xenobiotic metabolizing genes showed that carrying higher numbers of risk alleles was associated with increased vitiligo risk (9-16 vs 3-8 alleles: OR=2.79, P=0.00063), supporting a polygenic model for vitiligo involving detoxification pathway genes.

Case-control study of 169 omphalocele cases and 761 controls examining variants in folate, vitamin B12, and homocysteine metabolism genes. Variants in transcobalamin receptor (TCblR) rs2232775 (Q8R) and methylenetetrahydrofolate reductase (MTHFR) rs1801131 (1298A>C) were significantly associated with omphalocele (TCblR OR=3.20, p=0.0017; MTHFR OR=2.04, p=0.028). Additional race-ethnicity-specific associations were found with TCN2, BHMT rs3733890, and FOLH1 variants, suggesting disruption of methylation reactions as a potential risk factor.

This case-control study examined 29 polymorphisms in four folate-mediated one-carbon metabolism pathway genes (MTHFD1, SHMT1, MTHFR, DHFR) in Hispanic and non-Hispanic white populations to assess their association with conotruncal heart defects. MTHFD1 rs11627387 was associated with a 1.7-fold increased risk in both Hispanic mothers (OR=1.7, 95% CI=1.1-2.5) and Hispanic infants (OR=1.7, 95% CI=1.2-2.3). MTHFR rs1801133 (C677T) showed a 2.8-fold increased risk among Hispanic mothers with low dietary folate intake, while rs1801131 (A1298C) showed a 2.0-fold increased risk among those with higher folate intake. Gene-folate interactions were observed, suggesting maternal multivitamin use and dietary folate intake may modify conotruncal heart defect risk.

Case-control study (222 cases, 454 controls) examining gene-folate interactions in five folate-related genes (MTHFD1, MTHFR, SHMT1, DHFR, TYMS) and neural tube defect risk. Maternal MTHFR SNPs rs1476413, rs1801131, and rs1801133 showed decreased NTD risk with low folate intake (OR=0.55-0.69, 80% CI); infant MTHFD1 SNPs rs2236224, rs2236225, and rs11627387 showed increased risk (OR=1.53-4.25, 80% CI); maternal SHMT1 rs669340 showed protective gene-only effect (OR=0.69, 95% CI: 0.49-0.96).

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.

This meta-analysis of five Nordic samples (2,198 schizophrenia patients) investigated the association between the MTHFR C677T polymorphism (rs1801133) and age at onset of schizophrenia. While an initial Scandinavian study reported that the T-allele was associated with earlier disease onset (1.8 years per allele, P=0.007 in Copenhagen), replication in two independent Danish and Icelandic samples failed to confirm this finding (P=0.10 in Aarhus, P=0.86 in Iceland). The pooled meta-analysis of all five studies found no significant association (P=0.17, β=0.42 years per T-allele), concluding that the initial finding was likely due to chance rather than a true genetic effect.

This deep sequencing study of the MTHFR gene identified variants associated with myelomeningocele (a neural tube defect) in 96 affected subjects (49 Caucasian, 47 Mexican American). The authors discovered one novel intronic splice site variant (c.171+3G>T) and found seven SNPs with significant allele frequency differences compared to ethnically matched reference populations (p ≤ 0.05, Fisher's exact test), including five SNPs (rs13306561, rs2274976, rs2066462, rs12121543, rs1476413) not previously associated with neural tube defects.

A retrospective candidate gene association study of 136 lung cancer patients found that the MTHFR 1298A>C polymorphism (rs1801131) was associated with reduced risk of grade ≥2 radiation pneumonitis after thoracic radiation therapy (adjusted hazard ratio 0.37, 95% CI: 0.18-0.76, p=0.006). The SOD2 polymorphism (rs4880) and another MTHFR variant (rs1801133) showed no significant association with radiation pneumonitis risk.

This case-control study of 103 Mexican mothers of children with unilateral retinoblastoma and 97 control mothers found that maternal homozygosity for the DHFR 19bp deletion (rs70991108) was significantly associated with increased retinoblastoma risk (OR=3.78, 95% CI: 1.89-7.55; p=0.0002), even after adjusting for the child's genotype (OR=2.81, 95% CI: 1.32-5.99; p=0.0073). The association was stronger among mothers who took prenatal folic acid supplements (OR=3.58). Maternal MTHFR 677C>T polymorphism (rs1801133) was not associated with retinoblastoma risk.

This case-control study of 135 lung cancer patients examined associations between MTHFR polymorphisms (C677T rs1801133 and A1298C rs1801131), dietary folate intake, and DNA adducts in lung tissue. The A1298C variant (AC+CC) was associated with a 69.2% increase in lung DNA adducts (95% CI: 5.5%-171.5%), while the combined high-risk genotype (C677T CT+TT plus A1298C AC+CC) showed a 210.7% increase (95% CI: 21.4%-695.2%, P=0.02) in adducts. Low folate intake significantly exacerbated DNA damage in carriers of the A1298C variant, with 111.3% increased adducts among those with lowest tertile folate consumption.

This case-control association study examined genetic polymorphisms in 237 Russian women to identify variants associated with early reproductive loss and recurrent miscarriage. The study found that DNMT3B rs2424913 (OR=4.44-4.78), DNMT1 rs2228611 (OR=3.0-3.94), and DNMT1 rs8101626 (OR=2.5-3.1) were significantly associated with increased risk of sporadic and recurrent early pregnancy loss, while SYCP3 rs769825641 heterozygotes showed elevated risk of sporadic miscarriage.

This family-based association study examined 14 folate pathway genes using 89 SNPs in 445 NSCLP families (317 non-Hispanic White, 128 Hispanic) to identify genetic variants contributing to nonsyndromic cleft lip and palate. Evidence for association was found with SNPs in NOS3 and TYMS in the non-Hispanic White group (rs2373929/NOS3, rs502396/TYMS, and others), and with MTR, BHMT2, MTHFS, and SLC19A1 in the Hispanic group (rs1422086/BHMT2, rs2115540/MTHFS significant after Bonferroni correction). Multiple gene-gene interactions were detected, with CBS and MTHFD1 showing the most extensive interactions. Significant interactions were also found between several SNPs and maternal smoking and one SNP (rs651646/FOLR2) with offspring sex.

Comprehensive review evaluating SNPs as genetic predictors of choroidal neovascularization (CNV) response to photodynamic therapy with verteporfin (PDT-V). The paper examines pharmacogenetic correlations for thrombo-coagulative pathway variants (MTHFR rs1801133, F5 rs6025, F2 rs1799963, F13A1 rs5985), complement/inflammatory variants (CFH, HTRA1, CRP, ARMS2), and VEGFA variants (rs699947, rs2146323), concluding that specific SNPs show clinical plausibility as markers to optimize PDT-V efficacy and guide therapeutic approaches in neovascular macular degeneration.

Comprehensive review of genetic background in nonalcoholic fatty liver disease (NAFLD). The PNPLA3 I148M variant (rs738409 C>G) is identified as a major genetic player strongly associated with increased liver fat content, NASH development, fibrosis severity, and HCC risk. The TM6SF2 E167K variant (rs58542926) emerges as another key contributor to NAFLD pathogenesis and disease progression. Multiple additional GWAS-identified variants and candidate genes are reviewed for their roles in NAFLD susceptibility and progression.

This comprehensive review examines the genomics of schizophrenia and pharmacogenomics of antipsychotic drugs, synthesizing evidence on over 200 genes associated with psychotic disorders. The authors discuss five categories of genes relevant to antipsychotic response: disease-associated genes, mechanism-of-action genes, drug metabolism genes (particularly CYP2D6, CYP2C19, CYP2C9, CYP3A4), drug transporter genes, and pleiotropic genes. The review details pharmacogenomic profiles of 20+ antipsychotic drugs and demonstrates significant ethnic and interindividual variation in drug metabolism phenotypes, with examples including CYP2D6 extensive metabolizers (55.71% of population), intermediate metabolizers (34.7%), poor metabolizers (2.28%), and ultra-rapid metabolizers (7.31%).

A systematic review and meta-analysis of SNP associations with hepatocellular carcinoma (HCC) identified six SNPs in five genes with overall statistical significance. Two SNPs passed reliability criteria: rs1800562 (HFE, Cys282Tyr) with a recessive model OR of 5.20 (95% CI: 2.69-10.08) across 9 studies, and rs2279744 (MDM2) with an allele contrast OR of 1.57 (95% CI: 1.36-1.80) across 5 studies. Both were classified as having moderate epidemiological evidence by Venice guidelines.

This case-control and family-based study evaluated 64 SNPs in 34 genes for associations with spina bifida in 558 Irish case-families and 994 controls. Spina bifida was significantly associated with LEPR rs1805134 (GRR: 1.5, P = 0.0264) and COMT rs737865 (GRR: 1.4, P = 0.0206), with additional confirmations of previous findings in MTHFR 677C>T and other genes, suggesting roles for leptin signaling and methylation pathways in neural tube defect pathogenesis.

This case-control study examined 21 SNPs in 13 folate and choline metabolism genes for associations with tooth agenesis (hypodontia/oligodontia) in a Polish population of 159 cases and 185 controls. The CHDH gene variant rs6445606 showed the strongest association with a protective effect (OR=0.434, p=0.0004), with individuals carrying the C allele having reduced risk of tooth agenesis. Multifactor dimensionality reduction analysis revealed a significant epistatic interaction between CHDH rs6445606 and PLD2 rs3764897 (p=0.004).

This replication study analyzed three functional polymorphisms (MTHFR Ala222Val, LRP6 Ile1062Val, and LCT -13910C>T) in 944 postmenopausal Spanish women. Only MTHFR c.677C>T showed a significant association with vertebral fractures (OR=2.27, 95% CI 1.17-4.38, P=0.018), while LCT -13910C>T was associated with height and weight. No significant associations were found with lumbar spine or femoral neck bone mineral density.

Development and validation of a targeted NGS panel for diagnosing familial hemiplegic migraine (FHM), episodic ataxia type 2 (EA2), CADASIL, and migraine with aura. In 149 patients across 4 cohorts (55 FHM, 44 CADASIL, 31 EA2, 19 migraine families), the panel identified novel and known mutations in genes CACNA1A, ATP1A2, SCN1A, and NOTCH3, increasing mutation detection rate from 7.7% to 28.5%. Notably, ATP1A2 and NOTCH3 mutations were identified in typical migraine with aura families for the first time, demonstrating aetiological overlap with FHM.

This review examines molecular genetic factors and biochemical markers associated with migraine, including genes encoding ion channels (KCNK18/TRESK), neurotransmitter systems (SLC6A4, HCRTR1), and metabolic enzymes (MTHFR C677T, rs1801133). The authors discuss polymorphisms in MTHFR, KCNK18, HCRTR1, SLC6A4, STX1A, GRIA1, and GRIA3, and report preliminary data from 68 Polish participants (34 patients, 34 controls) showing associations between 5-HTTLPR and HCRTR1 rs2271933 polymorphisms with migraine susceptibility and biochemical markers including serotonin and hypocretin-1 levels.

This case-control study examined folate pathway gene variants in 121 DS-AVSD cases and 122 DS controls (no CHD). Tag SNPs in MTHFR, MTR, MTRR, CBS, and SLC19A1 were genotyped. SLC19A1 showed significant gene-level association with atrioventricular septal defect (P=0.01), with multiple tag SNPs nominally associated (OR 1.08-1.72). All significant SLC19A1 SNPs showed strong LD (r²≥0.80) with the nonsynonymous variant rs1051266 (c.80A>G, p.H27R). MTHFR c.1298A was over-transmitted to cases (P=0.05) and under-transmitted to controls (P=0.02), showing association in FBAT analysis (P=0.03 dominant, P=0.01 additive). These results suggest folate pathway disruption contributes to AVSD risk in Down syndrome individuals.

This Japanese cohort study of 206 elderly women (mean age 69.7 years) from the Obuse registry investigated associations between genetic variants and osteoarthritis (OA) prevalence. LRP5 rs3736228 showed significant associations with knee/hip OA (OR 7.28, 95% CI 2.22-28.08) and osteoporosis (OR 5.24, 95% CI 0.95-26.98). MTHFR rs1801133 showed a protective association with knee OA prevalence (OR 0.58, 95% CI 0.35-0.97). Other variants (LRP5 rs312009, GDF5 rs143383, SMAD3 rs12901499) showed no significant associations.

A pathway-wide association study in 425 case-parent triads examined 109 SNPs in 29 folate/one-carbon metabolism genes and 68 SNPs in 16 vitamin A metabolism genes for associations with cleft lip/palate (CL/P) and cleft palate only (CPO). Despite strong epidemiologic evidence that folic acid and vitamin A reduce cleft risk, no convincing genetic associations were found; the strongest association was FOLH1 with CPO (p=0.0008), but findings were fewer than expected by chance and inconsistent with protective effects of vitamin supplementation, suggesting vitamin metabolism gene polymorphisms do not play an etiologic role in oral facial clefts.

This longitudinal study of 5,167 Japanese community-dwelling adults (aged 40-84 years) examined the association between MTHFR C677T (rs1801133) and MTR A2756G (rs1805087) polymorphisms and age-related hearing impairment. The MTHFR 677T allele was significantly associated with reduced hearing impairment risk (OR: 0.7609, 95% CI: 0.6178-0.9372) only in individuals with MTR AA genotype. The favorable effect of the MTHFR 677T allele was independent of folate and homocysteine levels, while elevated homocysteine was independently associated with increased hearing impairment risk.

A case-control study of 1,097 renal cell carcinoma (RCC) cases and 1,555 controls in Central and Eastern Europe examined common genetic variation in 5 folate metabolism genes. Variants in MTHFR (A222V rs1801133) and TYMS (IVS2-405C rs502396) were significantly associated with RCC risk, with the MTHFR variant increasing risk (OR=1.44) particularly in groups with low vegetable intake, while TYMS variant reduced risk (OR=0.73). The associations demonstrated significant gene-nutrient interactions with vegetable consumption.

This study characterized an Ashkenazi Jewish (AJ) population-specific genetic signature using genome-wide SNP data from 1,312 AJ individuals. Using ADMIXTURE and principal components analysis, the authors identified allelic patterns that differentiate AJ from European and Middle Eastern populations. Gene Ontology enrichment analysis of the AJ-specific genetic signature revealed enrichment in genes involved in transepithelial chloride transport (including CFTR with rs213950 showing V158M variant) and equilibrioception (PCDH15, CLRN1), implicating these pathways in the elevated prevalence of cystic fibrosis and Usher syndrome in Ashkenazi Jews. The study also identified disease-relevant alleles including MTHFR C677T (rs1801133), SH2B3 rs3184504 associated with type 1 diabetes/celiac disease, and MC1R rs1805005, and provided a validated set of 103 ancestry informative markers (AIMs) for population stratification correction.

Case-control study of 536 cleft lip with/without cleft palate (CLP) cases and 426 cleft palate only (CPO) cases in Ireland, testing four folate metabolism gene SNPs. MTHFD1 1958 G→A showed maternal risk associations with CPO (OR 1.50, p=0.02) and CLP (OR 1.38, p=0.03). MTHFR 677 C→T showed maternal risk for CPO (OR 1.50, p=0.03). MTHFR 1298 A→C and TC II 776 C→G showed no significant associations.

A candidate gene association study of 6,752 women from the Study of Osteoporotic Fractures examined 31 polymorphisms in 18 candidate osteoporosis genes for associations with fracture risk and bone mineral density. ALOX15_G48924T (rs7220870) T/T genotype was associated with 33% higher hip fracture risk (HR=1.33, 95% CI 1.00-1.77); PRL_T228C (rs7739889) C alleles reduced nonvertebral fracture risk by ~20%; BMP2_A125611G (rs235764) G/G showed 51% higher vertebral fracture risk (OR=1.51, 95% CI 1.03-2.23); and MMP2_C595T (rs243865) T allele carriers had reduced vertebral fracture risk. No significant associations were found with total hip BMD.

This pharmacogenetics study analyzed 28 SNPs in methotrexate (MTX) metabolism genes (SLC19A1/RFC1, ABCB1, FPGS, GGH) in two Spanish populations with rheumatoid arthritis (n=124 and n=194). Key findings: FPGS rs10987742 and rs10106 associated with MTX response (p=0.033, p=0.041); FPGS rs10106 also associated with MTX survival (p=0.005) and toxicity (p=0.021); ABCB1 rs868755, rs10280623, rs1858923 associated with toxicity (p=0.025, p=0.048, p=0.031). In the first study, MTHFR rs17421511 (p=0.024) and rs1476413 (p=0.0086) associated with response, DHFR rs1643650 (p=0.026) associated with response, ATIC rs16853826 associated with toxicity (p=0.039).

This pharmacogenetic study examined genetic variants in the folate metabolism and MTX transport pathways in rheumatoid arthritis patients receiving methotrexate monotherapy. Study 1 (n=124) identified rs17421511 and rs1476413 in MTHFR and rs1643650 in DHFR as significantly associated with MTX treatment response (p=0.024, p=0.0086, p=0.026 respectively), and rs16853826 and rs10197559 in ATIC as associated with toxicity (p=0.039). Study 2 (n=194) found rs10106 and rs10987742 in FPGS associated with response, and rs868755, rs10280623, rs1858923 in ABCB1 associated with toxicity, with rs10106 also associated with longer MTX monotherapy survival.