These findings support further investigation of HNF4A-related lipid pathways and require replication in independent Chinese and multi-ancestry cohorts before genetic and lipid profiles can be considered for T2D risk stratification.
Abstract
Background/Objectives: To evaluate the association between HNF4A rs4812829 and type 2 diabetes (T2D) in a rural Chinese population and to investigate its interaction with blood lipids in the association. Methods: A total of 4496 participants free of diabetes at baseline from a family-based cohort in rural China were included. Demographic, lifestyle, and medical history data were collected via standardized questionnaires. Anthropometric and biochemical measurements were performed using standardized protocols and automated assays on fasting blood samples. Mixed-effects Cox proportional hazards models, accounting for familial clustering, were employed to examine the association between HNF4A rs4812829 and incident T2D risk. Additionally, multiplicative interaction terms were used to assess interactions. Results: After a median follow-up of 10.76 years, 895 incident T2D cases were identified. Under an additive genetic model, each additional G allele of rs4812829 was significantly associated with an increased risk of T2D (HR 1.38, 95% CI 1.19–1.59). A significant multiplicative interaction was observed between rs4812829 and HDL-C (p = 0.004). In genotype-stratified analyses, higher HDL-C levels were strongly associated with lower T2D risk among AA homozygotes (HR 0.04, 95% CI 0.003–0.43) and AG heterozygotes (HR 0.30, 95% CI 0.10–0.84), but not among GG homozygotes (HR 1.32, 95% CI 0.35–4.91). Conclusions: This study finds HNF4A intronic variant rs4812829 is significantly associated with the incident T2D risk in a rural Chinese population, and this association exhibits an interaction with HDL-C levels. These findings support further investigation of HNF4A-related lipid pathways and require replication in independent Chinese and multi-ancestry cohorts before genetic and lipid profiles can be considered for T2D risk stratification.
BACKGROUND
Type 2 diabetes (T2D) affects 11.1% of the global population, underscoring the need for biomarkers that help characterize glycemic control status among treated individuals. We evaluated the association between the FTO variant rs9939609‑A and glycemic control in a Mexican population.
METHODS
A total of 174 individuals living with T2D from Mérida and Sisal, Yucatán, were included, of whom 85% were receiving oral hypoglycemic agents as main treatment. Glycemic control was defined cross‑sectionally as good (≤ 130 mg/dL, n = 63) or poor (> 130 mg/dL, n = 111) with fasting glucose. Linear mixed models incorporating relevant covariates and a family random intercept were used. Effect size estimates were transformed to logit odds ratios.
RESULTS
After adjustment for age, sex, BMI, years since T2D diagnosis, and treatment, the minor allele of rs9939609 (A) was associated with an increased risk of poorer glycemic control, reaching significance under both the additive (OR = 1.145 [1.003-1.307], p = 0.047) and recessive (OR = 1.514 [1.026-2.234], p = 0.038) models. In an alternative model adjusting for waist circumference instead of BMI, the effect of rs9939609‑A in the additive model was slightly attenuated (OR = 1.135 [0.994-1.297], p = 0.063), while the recessive model remained significant (OR = 1.486 [1.010-2.189], p = 0.046).
CONCLUSIONS
rs9939609-A was associated with poorer glycemic control in this exploratory cohort, but replication in larger and ancestrally characterized samples is required.
N. Fragoso-Bargas, R. V. Escarcega-Castro, I. Quintal-Ortiz et al.· BMC Research Notes· 0 citations
INTRODUCTION
Genetic polymorphisms affecting oxidative stress and lipid metabolism contribute to type 2 diabetes (T2D). The role of oxidized low-density lipoprotein receptor 1 (OLR1) rs11053646 single nucleotide polymorphism (SNP) in the Saudi population remains unclear. This study aimed to assess its association with T2D risk in Saudi adults.
METHODS
A tertiary hospital-based case-control study was conducted among 143 Saudi adults (≥18 years) in Riyadh from November 2019 to January 2020, including 79 individuals with T2D (fasting blood glucose ≥7 mmol/L) and 64 normoglycemic controls (<5.6 mmol/L). Genomic DNA was extracted from peripheral blood, and the OLR1 rs11053646 SNP was genotyped using PCR-RFLP. Genotype distributions were tested for Hardy-Weinberg equilibrium (HWE). Logistic regression models adjusted for age, sex, and body mass index were used to estimate odds ratios (ORs) with 95% confidence intervals (CIs).
RESULTS
Genotype distribution in controls conformed to HWE (p=0.14). The GG genotype was predominant, while the CC genotype was absent. GC frequency was slightly higher in T2D cases, but not statistically significant. Allele distributions were comparable between groups. Adjusted analysis showed no significant association with T2D risk (OR=0.41, p=0.14).
DISCUSSION
OLR1 rs11053646 SNP was not significantly association with T2D risk in this Saudi cohort. The absence of the CC genotype and small sample size may have limited statistical power to detect potential associations.
CONCLUSION
OLR1 rs11053646 SNP does not appear to be associated with T2D risk in Saudi adults. Larger studies are required to confirm these findings.
V. Vennu· Endocrine, Metabolic & Immun...· 0 citations
Background
Type 2 diabetes mellitus (T2DM), and coronary artery disease (CAD) are metabolically related lesions with
dyslipidemia and the deficiency of cholesterol transportation. ABCA1 is a key gene in HDL metabolism, and its
polymorphisms could act as cardiometabolic risk factors.
Objective
The study needed to examine how ABCA1 (rs1800977 and rs1800976) polymorphisms relate to T2DM and
CAD, as well as to both in a North Indian cohort.
Methods
Case control study was done on 600 participants (controls, T2DM, CAD, T2DM+CAD; n=150 each). PCRRFLP was used to carry out genotyping. Statistical tests were chi-square tests, odds ratios (ORs), and haplotype
analysis.
Results
There was no significant relationship with rs1800977. Conversely, the association between the two diseases
(CAD and T2DM+CAD) with the association of a strong association with the frequency of G allele and the GG
genotype was observed in the case of rs1800976 (OR=3.11 and 2.58, respectively; p<0.05). The high
triglycerides and low HDL-C were associated with risk genotypes, and CG and TG were haplotypes of risk.
Conclusion
The polymorphism at the site (rs1800976) was greatly linked to higher forms of CAD and T2DM+CAD
indicating that the site could serve as a genetic marker of cardiometabolic risk.
Vikas Kumari, Nisha Khola, Rajan Sharma et al.· International Journal of Dru...· 0 citations
Background. Polymorphisms of the TCF7L2 gene are among the most important genetic risk factors for type 2 diabetes mellitus (T2DM); however, their role in the development of diabetic kidney disease (DKD) remains insufficiently understood.Objective. To evaluate the association between the TCF7L2 rs12255372 polymorphism and the risk of type 2 diabetes mellitus, as well as its relationship with renal function.Materials and Methods. The study included 86 patients with T2DM and 24 healthy controls. Genotyping of the TCF7L2 rs12255372 polymorphism was performed using polymerase chain reaction. Allele and genotype distributions were analyzed together with renal function parameters, including estimated glomerular filtration rate (eGFR), urea, creatinine, nephrin, and cystatin C.Results. The T allele was significantly more frequent in patients than in controls (29.7% vs. 2.1%; OR=19.8; 95% CI: 4.54–86.37; p=0.01). Carriers of the TT genotype demonstrated a significantly lower eGFR (74.8±3.24 mL/min/1.73 m²; p<0.01) and higher serum urea levels (7.90±1.28 mmol/L; p<0.05) compared with carriers of the GG and GT genotypes. Although differences in nephrin and cystatin C levels were not statistically significant, an increasing trend was observed among TT carriers.Conclusions. The TCF7L2 rs12255372 polymorphism, particularly the T allele, is associated with an increased risk of type 2 diabetes mellitus and early renal dysfunction. This genetic variant may serve as a promising molecular marker for early risk stratification of diabetic kidney disease.
Z.A. Raximberdiyeva· Journal of modern medicine· 0 citations
Objectives: Coronary artery disease (CAD) remains a leading cause of morbidity and mortality worldwide, yet population-specific evidence regarding the contribution of MIA3 genetic variation in Middle Eastern populations remains limited. This study investigated the association of the MIA3 rs17465637 polymorphism with CAD susceptibility and its relationship with lipid-related phenotypes in a Saudi population. Methods: A case–control study was conducted between June 2020 and August 2022, including 200 patients with angiographically confirmed CAD and 200 age- and sex-matched healthy Saudi controls. Genotyping of rs17465637 was performed using a TaqMan real-time polymerase chain reaction assay. Genotype distributions were evaluated using chi-square analysis under multiple inheritance models. Multivariable logistic regression was subsequently performed to estimate adjusted odds ratios after controlling age, BMI, smoking, physical inactivity, systolic BP, diastolic BP, blood glucose, triglycerides, total cholesterol, LDL-C, and HDL-C. Associations between rs17465637 genotypes and serum lipid parameters were also examined. Results: Genotype frequencies of rs17465637 differed modestly between cases and controls; however, unadjusted comparisons under codominant, dominant, recessive, and allelic inheritance models did not reach statistical significance, and none remained significant after Bonferroni correction. In contrast, multivariable logistic regression demonstrated an independent association between the rs17465637 C allele and CAD after adjustment for conventional cardiovascular risk factors. In genotype–phenotype analyses, carriers of the C allele exhibited higher association with low-density lipoprotein cholesterol concentrations and less favorable lipid profiles than AA homozygotes, supporting a relationship between the variant and lipid metabolism. These findings are consistent with a potential contribution of rs17465637 to CAD susceptibility through lipid-related pathways. Conclusions: Although unadjusted genotype comparisons were not statistically significant after correction for multiple testing, multivariable analysis provides evidence supporting an independent association between the MIA3 rs17465637 variant and CAD susceptibility in this Saudi cohort. The observed associations with adverse lipid profiles further provide evidence linking this specific locus to the molecular mechanisms underlying cardiovascular disease. Replication in larger, multi-center studies incorporating genome-wide ancestry-informative markers and functional investigations is warranted to further minimize the possibility of residual population stratification, confirming these findings and clarifying the biological mechanisms underlying this association.
N. Bogari, Samar N. Ekram, Amr A. Amin et al.· Diagnostics· 0 citations
Introduction Type 2 diabetes (T2D) is a significant metabolic disorder with disproportionately high burden in obese South Asian populations, yet not all obese individuals develop the disease. This study identified the metabolic, inflammatory, and pharmacological markers associated with prevalent T2D in obese Indians using age- and sex-matched case-control analysis. Methods A matched-pair analysis was performed on 514 age- and sex-matched pairs with and without T2D. Patients had obesity [body mass index (BMI) 25–45 kg/m², aged 20–75 years] and participated in a one-year lifestyle intervention program in India. Anthropometric, biochemical markers and medical history were analyzed. Homeostatic model assessment for insulin resistance (HOMA2IR) and beta-cell function (HOMA2%B) was calculated. Significant markers were incorporated into a logistic regression model and temporally validated in an independent time-cohort (n=966). Performance was evaluated through discrimination [receiver operating characteristics area under the curve (ROC-AUC)], calibration, and decision curve analysis. A nomogram was constructed based on the logistic regression model. Results Median age and BMI were 46 (IQR 12) years and 29.7 (IQR 5.5) kg/m². Key markers associated with prevalent T2D were poor beta-cell function (HOMA2%B ≤50; OR = 40.9, 95% CI: 24.5–68.2), insulin resistance (HOMA2IR ≥2; OR = 4.5, 95% CI: 3.0–6.7), low HDL-C (OR = 2.1, 95% CI: 1.5–3.0), elevated hsCRP ≥3 mg/L (OR = 1.9, 95% CI: 1.4–2.7), Obesity Class I (BMI 25.0–29.9 kg/m²; OR = 2.1, 95% CI: 1.5–2.9), and antihypertensive medication use (OR = 1.7, 95% CI: 1.2–2.4). Model discrimination was good (AUC 0.860 development, 0.865 validation, both p<0.001). The Hosmer-Lemeshow test showed good model fit (p=0.562). Isotonic-calibrated Models 1 and 2 had Brier scores 0.14 and 0.162, indicating acceptable calibration. Decision curve analysis confirmed net clinical benefit across threshold probabilities 0.10–0.85. Conclusion This study identified and temporally validated key metabolic and clinical markers associated with prevalent T2D, demonstrating good discrimination (AUC 0.860) in obese Indian individuals. External validation and prospective evaluation are needed before clinical application.
Anagha Vyawahare, Pramod Tripathi, Nidhi Kadam et al.· Frontiers in Clinical Diabet...· 0 citations