rs1801282

This association study examined 43 diabetes-related SNPs in relation to diastolic dysfunction and cardiovascular disease across two Swedish cohorts. HNF1B rs757210 (T-allele) was the main finding, associated with prevalent diastolic dysfunction in both the discovery cohort (MPP-RES; OR 1.21, P=0.024) and replication cohort (VARA; OR 1.38, P=0.042), and with increased risk of incident CVD (HR 1.05, P=0.042) but not CHF over 30+ years of follow-up.

A literature review of 70 studies examining single nucleotide polymorphisms (SNPs) associated with obesity in Mexican populations published 2011-2021. The authors identified SNPs with differential behavior in Mexican compared to Caucasian populations, including rs17782313 (MC4R), rs6548238 (TMEM18), rs6265 (BDNF), rs7498665 (SH2B1), and notably rs6232 (PCSK1) associated with early-onset obesity in Mexican youth. The review emphasizes ethnicity-dependent genetic effects on BMI heritability (40-70%) and highlights genes involved in cholesterol metabolism and adipokine signaling pathways.

This case-control association study examined 13 PPAR-γ gene SNPs in 303 sepsis patients and 303 controls from North China Han population. Three SNPs showed significant associations: rs1801282 (Pro12Ala) with decreased sepsis risk (OR=0.55, p=0.024), rs2972164 with increased sepsis risk (OR=1.74, p=0.03), and rs4135275 with increased severe organ dysfunction (OR=2.66, p=0.038). The TAT haplotype (rs2972164-rs4684846-rs17036188) was associated with increased sepsis risk (OR=1.66, p=0.038).

Family-based study examining parent-of-origin effects (POE) on type 2 diabetes risk in 4,211 individuals from Botnia and 1,463 from the Hungarian Transdanubian Biobank. Three loci showed nominal POE, with the strongest signal at rs7578597 in THADA showing excess maternal transmission of the risk T allele to diabetic offspring (Botnia pPOE=0.01, HTB pPOE=0.045, combined pPOE=0.0006). Five CpG sites flanking rs7578597 showed differential methylation between diabetic and non-diabetic islets, supporting potential THADA imprinting. Meta-analysis confirmed association with type 2 diabetes (OR=1.24, 95% CI 1.12-1.36, p=1.96×10⁻⁵).

Case-control study of 518 type 2 diabetes cases and 518 controls in a Karnataka (Indian) population examined the association of three SNPs with T2D susceptibility and obesity. PPAR-γ2 rs1801282 and FTO rs9939609 were significantly associated with T2D in the overall sample (OR=1.42, P=0.02 and OR=1.19, P=0.01 respectively), with effects primarily observed in the obese diabetic subgroup. ADIPOQ rs16861194 showed no significant association (OR=1.08, P=0.39). A meta-analysis of 22 studies on PPAR-γ2 and FTO variants in Asian populations confirmed FTO's significant risk association with T2D.

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.

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.

This case-control study of 300 Pakistani individuals (150 RA cases, 150 controls) found a significant association between the PPARG Pro12Ala variant (rs1801282) and rheumatoid arthritis. The homozygous GG (AlaAla) genotype was significantly more common in cases (18.0%) versus controls (3.3%; χ² = 18.54, p < 0.0001), with the G allele showing increased frequency in cases (OR = 1.991, 95% CI = 1.412-2.808, p < 0.0001).

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).

This systematic study screened 18 T2D-associated SNPs and 5 environmental factors (trans-β-carotene, cis-β-carotene, γ-tocopherol, heptachlor epoxide, PCB170) for gene-environment interactions using NHANES data (1999-2000, 2001-2002). The strongest interaction was between rs13266634 (SLC30A8) and trans-β-carotene: in subjects with low trans-β-carotene levels, the per-risk-allele OR was 1.8 (95% CI 1.3-2.6), 40% higher than the marginal effect, and this interaction withstood Bonferroni correction (p = 0.006, FDR 1.5%). Four interactions total achieved FDR < 20%, suggesting that nutrient levels modify genetic risk for T2D.

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).

Of 40 SNPs previously associated with type 2 diabetes, 19 (48%) introduce or remove CpG sites. In 84 human pancreatic islet donors, all 16 analyzed CpG-SNPs showed statistically significant differential DNA methylation (p≤2.3×10⁻⁵). Several CpG-SNPs including rs391300 (SRR), rs5945326 (DUSP9), rs11708067 (ADCY5), rs5015480 (HHEX), rs13266634 (SLC30A8), rs1801214 (WFS1), rs564398 (CDKN2A), and rs2237895 (KCNQ1) were associated with differential gene expression, alternative splicing, or hormone secretion, suggesting DNA methylation-mediated mechanisms linking genetic variants to type 2 diabetes pathogenesis.

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.

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.

This case-control study in north India investigated associations of PPARγ gene polymorphisms (Pro12Ala rs1801282 and C1431T rs3856806) with obesity in 642 subjects (309 obese, 333 nonobese). Pro12Ala variants showed significant association with increased obesity risk (OR 1.655, 95% CI 1.155-2.370, P=0.006) and higher insulin, HOMA-IR levels, plus lower adiponectin. C1431T showed no significant obesity association. The findings suggest PPARγ polymorphisms influence obesity through insulin resistance mechanisms in this Indian population.

This case-control association study examined four PPARG polymorphisms in a Hungarian IBD cohort (575 CD, 103 UC patients, 486 controls). The Pro12Ala variant (rs1801282) showed significant protective effect in CD homozygotes (OR=0.33, P=0.03), and haplotype analysis revealed the GAGG haplotype was protective in both CD and UC (OR=0.14 in UC, P=3.78×10⁻⁵), while the GAGC haplotype increased UC risk (OR=6.70, P=3.85×10⁻¹⁰).

Association analysis of 31 GWAS-confirmed type 2 diabetes SNPs in 3,089 Indian sib pairs (2,528 for quantitative traits, 561 for diabetes) identified significant associations with intermediate traits: CDKAL1 rs7756992, TCF7L2 rs7903146 and rs12255372 with fasting glucose (β=0.009-0.01, p≤0.01); ADAM30 rs2641348, NOTCH2 rs10923931, TCF-2/HNF1B rs757210, and CDKN2A/B rs10811661 with fasting insulin and HOMA-IR (β=±0.05-0.09, p≤0.05); and THADA rs7578597 with type 2 diabetes (OR 1.5, p=0.03).

This association study identified rs10811661 near CDKN2A/B on chromosome 9p21, a type 2 diabetes risk SNP, as significantly associated with diabetic nephropathy in 2,963 type 1 diabetes patients (OR 1.33, p=0.00045). The association was replicated in meta-analysis across four cohorts (n>5,000; OR 1.15, p=0.011) and was particularly strong for end-stage renal disease (OR 1.35, p=0.00038). The SNP was also associated with severe retinopathy but not cardiovascular disease.

This case-control study analyzed 7 SNPs in 6 genes previously associated with type 2 diabetes (T2DM) in 235 kidney transplant patients medicated with tacrolimus to determine their effect on new-onset diabetes after transplantation (NODAT). While no individual SNP showed significant association with NODAT, patients carrying >7 of the 14 'diabetogenic' alleles had significantly higher NODAT risk (OR 2.17, 95% CI 1.18–3.99, p=0.015), particularly for late-onset NODAT (OR 1.37 per allele, 95% CI 1.05–1.78, p=0.017).

A randomized controlled intervention study in 68 obese men tested the effects of polyphenol-rich cloudy apple juice (750 mL/day for 4 weeks) on obesity-related markers and diet-gene interactions. Cloudy apple juice significantly reduced percent body fat (Δ: -1.0 ± 1.3% vs control -0.2 ± 0.9%, p < 0.05) and increased lean body mass. The IL-6-174 G/C polymorphism (rs1800795) showed significant interaction with body fat reduction: only C/C carriers showed significant fat loss with apple juice consumption (p = 0.011 for interaction), while G/C and G/G carriers did not respond.

Population-based study of 6,733 non-diabetic Finnish men examining associations between 19 confirmed type 2 diabetes risk loci and tissue-specific insulin resistance indices. Type 2 diabetes risk SNPs in KCNJ11 (rs5219) and HHEX (rs1111875) showed significant associations with lower liver insulin resistance (p<0.0013 and p=5.4×10⁻⁵, respectively), while the Pro12 allele of PPARG2 (rs1801282) was significantly associated with higher adipocyte insulin resistance (p=6.2×10⁻⁵).

This association study analyzed four T2D-related SNPs (rs5219, rs1801282, rs7903146, rs12255372) in 26 Yakut patients with type 2 diabetes via pyrosequencing. No statistically significant differences were found between Yakut T2D cases and control groups for KCNJ11, PPARG, or TCF7L2 polymorphisms. The study identified strong linkage disequilibrium between TCF7L2 rs7903146 and rs12255372 (D'=1, LOD=4.92) in Yakuts and demonstrated that the risk T-allele frequency of TCF7L2 SNPs is notably lower in Asian populations (3.8% in Yakuts, 2-3% in Japanese and Chinese) compared to European and African populations.

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 study evaluated the utility of genomic profiling combining multiple low-penetrance variants for colorectal cancer (CRC) risk prediction and screening. Using simulations and ARCTIC study data (1,257 cases, 1,336 controls), the authors found that 140-160 common risk variants (OR ~1.2 each) would be needed to capture 80% of CRC cases in the top 50% of individuals by genetic risk score. In empirical analysis, a panel of replicated variants (rs1801282, rs2289046, rs2472300, rs3099844, rs4779584, rs10505477, rs10735810) achieved modest predictive value (AUC 0.54-0.66 with age/sex), with subjects carrying 30+ risk alleles showing 2.26-fold increased risk (95% CI 1.27-4.04) versus those with ≤20 alleles.

This association study of 4,213 Danish individuals examined 25 type 2 diabetes risk variants and their association with birthweight. The study found that type 2 diabetes risk alleles near ADCY5 (rs11708067, β = -33 g, p = 0.004), CDKAL1 (rs7756992, β = -22 g, p = 0.04), and HHEX-IDE (rs1111875, β = -16 g in meta-analysis, p = 8×10⁻⁵, n = 25,164) were associated with reduced birthweight, supporting the fetal insulin hypothesis. Meta-analyses confirmed these associations and showed no strong general effect on birthweight from the 25 common type 2 diabetes risk alleles combined.

The HERITAGE Family Study examined eight type 2 diabetes susceptibility variants in 481 sedentary individuals undergoing 20-week endurance training. PPARG rs1801282 (Pro12Ala) was the only significant finding: Ala carriers showed greater improvements in glucose tolerance (p=0.0008), glucose effectiveness (p=0.004), and disposition index (p=0.003) in response to exercise training, though no associations were found with other recently identified GWAS variants.

This study tested association between 10 tagging SNPs in PPARG (peroxisome proliferator-activated receptor-gamma) and peak bone mineral density (BMD) in 401 Chinese nuclear families using quantitative transmission disequilibrium test (QTDT), plus 710 postmenopausal women. The study found no significant association between PPARG polymorphisms and BMD at the lumbar spine or femoral neck in the family-based analysis, though rs1801282 showed association with BMD at lumbar spine in postmenopausal women (P=0.013).

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.

This case-control and family-based association study tested whether 18 type 2 diabetes susceptibility loci are associated with type 1 diabetes in 7,606 type 1 diabetic cases and 8,218 controls. Only PPARG (rs1801282/Pro12Ala, OR=0.91, p=0.004) and HHEX-IDE (rs1111875, OR=0.94, p=0.003) showed evidence of association with type 1 diabetes. The authors conclude that type 1 and type 2 diabetes do not share a common genetic background, supporting the view that type 1 diabetes is primarily an autoimmune disease.

Replication study of 7 meta-analysis-derived type 2 diabetes susceptibility SNPs in 6,244 Japanese individuals across 3 independent populations. Only rs864745 in JAZF1 showed nominal association (OR 1.148, 95% CI 1.034-1.275, p=0.0098) but not after Bonferroni correction; other loci did not reach statistical significance, suggesting these European-identified variants have minor or absent effects in Japanese populations.

This study tests the thrifty genotype hypothesis by examining 17 confirmed type 2 diabetes susceptibility loci and 13 obesity-susceptibility loci for signatures of positive selection. Using ancestral/derived allele analysis, integrated haplotype scores (iHS), and population differentiation (FST), the authors found limited evidence supporting the thrifty genotype hypothesis. Only rs7901695 at TCF7L2 showed notably elevated FST values (0.579 between JPT+CHB and YRI populations), and FTO showed the strongest selection signal among obesity loci (iHS=1.991).

This case-control study of 1,423 Russian athletes and 1,132 controls examined 15 metabolic gene polymorphisms associated with elite endurance athlete status. Ten 'endurance alleles' were identified: rs4253778 (PPARA), rs2016520 (PPARD), rs8192678 (PPARGC1A), rs7732671 (PPARGC1B), rs1937 (TFAM), rs660339 (UCP2), rs1800849 (UCP3), rs2010963 (VEGFA), NFATC4 rs2229309, and PPP3R1 promoter 5I. The proportion of subjects with ≥9 endurance alleles was significantly higher in elite endurance athletes versus controls (85.7% vs 37.8%, P=7.6×10⁻⁶). The number of endurance alleles positively correlated with slow-twitch muscle fiber proportion (r=0.50, P=4.0×10⁻⁴) and maximal oxygen consumption (r=0.46, P=7.0×10⁻⁴).

Nested case-control study of 258 prostate cancer cases and 258 matched controls in the CLUE II prospective cohort examining genetic variants in inflammation and obesity-related genes. The IL10 -1082G>A variant (rs1800896, A allele) was positively associated with prostate cancer risk (AG vs GG: OR=1.69, 95% CI 1.10-2.60; AA vs GG: OR=1.81, 95% CI 1.11-2.96), while a TLR4 variant (rs4986790) showed inverse association, and no consistent associations were found for obesity-related gene variants.

This case-control study in 869 Korean women with gestational diabetes mellitus (GDM) and 632 non-diabetic controls examined whether type 2 diabetes-associated genetic variants discovered in recent GWAS are also associated with GDM. Multiple variants showed significant associations with GDM, including rs7756992 and rs7754840 in CDKAL1 (OR 1.55, p=4.17×10⁻⁹), rs10811661 in CDKN2A-CDKN2B (OR 1.49, p=1.05×10⁻⁷), variants in HHEX, rs4402960 in IGF2BP2 (OR 1.18, p=0.03), rs13266634 in SLC30A8 (OR 1.24, p=0.005), and rs7903146 in TCF7L2 (OR 1.58, p=0.038).

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 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.

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 comprehensive review article traces the evolution of pharmacogenetics from single-gene analysis to whole-genome approaches. It discusses validated pharmacogenetic biomarkers with clinical impact including CYP2D6, CYP2C9, CYP2C19, TPMT, DPD, VKORC1, UGT1A1, and ADRB1/ADRB2, providing examples of how genetic variants affect drug metabolism and response. The paper emphasizes the importance of integrating pharmacogenetic information into clinical practice and drug development.

Case-control study of 273 T2DM patients and 343 controls in the Tunisian population examined three GLUT1 SNPs (rs710218, rs841847, rs841853). The XbaI SNP (rs841853) GT genotype conferred increased T2DM risk (OR=2.4), and the TAT haplotype combining all three SNPs showed the strongest association with T2DM susceptibility (OR=3.4).

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 case-control association study in 864 Japanese type 2 diabetes patients and 864 controls confirmed that three SNPs in HHEX (rs5015480 OR=1.46, rs7923837 OR=1.40, rs1111875 OR=1.30) were significantly associated with type 2 diabetes across ethnic groups. SNPs in FTO, CDKAL1, CDKN2B, and SLC30A8 showed nominal associations, while several SNPs were associated with impaired pancreatic beta cell function measured by HOMA-beta index.

This journal issue contains multiple genetic association studies on rheumatoid arthritis (RA). A key REMARCA study (146 aCCP+ RA patients vs 314 controls) identified polymorphisms in CTLA4 (rs231775 +49A/G), IL10 (rs1800872 -592A/C), and IL6R (rs8192284 +358A/C) associated with high inflammatory disease activity, with CTLA4 and IL10 minor alleles showing increased risk (OR=1.4, p=0.02 and OR=1.9, p<0.0001 respectively) and IL6R minor allele being protective (OR=0.7, p=0.03). A separate study analyzed NOS3, PPARG, PPARGC1A, PPARGC1B and PAI1 polymorphisms in 73 RA patients for cardiovascular risk.