2026· passer of basic and applied sciences· 0 citations· 31 references
TL;DR
It is concluded that no detectable association was found between the TMPRSS6 rs1421312 SNP and IDA, and no detectable associations were found with Hepcidin levels, sTfR1, or the sTfR1-Ferritin Index.
Abstract
Background : Iron deficiency anemia (IDA) continues to pose a significant global health problem affecting diverse demographic groups worldwide. A complex interplay between environmental and genetic factors affects the development of IDA. In this context, Variation in TMPRSS6 gene has been identified as a potential risk factor. This study examines the association between TMPRSS6 rs1421312 SNPs and key biomarkers of iron deficiency status. These included hepcidin, soluble Transferrin Receptor Type 1 (sTfR1), and the sTfR1-F Index, among non-pregnant women of reproductive age. Methodology : To explore these associations, a cross-sectional design was employed. A total of 140 non-pregnant women, aged 17-50 years, were recruited based on low MCV and MCH. Participants were grouped into 60 IDA cases and 80 non-IDA cases based on a comprehensive analysis of their complete blood counts and serum iron studies. Additionally, DNA extraction and genotyping were carried out using allele-specific primers through PCR. Result: The distribution of genotypes for TMPRSS6 rs1421312 in cases without IDA (non-IDA) was 9(11.25%) (CC), 67(83.75%) (TC), and 4(5%) (TT). Whereas in cases with IDA, it was 8(13.33%) (CC), 48(80%) (TC), and 4(6.66%) (TT). No significant difference was found between the groups (P = 0.840). Additionally, the results indicated that the variations in Hepcidin levels, sTfR1, and the sTfR1-Ferritin Index among the CC, TT, and TC genotypes were not statistically significant. Conclusion: To the best of our knowledge, this represents the first such report from an Iraqi population. The current study concluded that no detectable association was found between the TMPRSS6 rs1421312 SNP and IDA. Additionally, no detectable associations were found with Hepcidin levels, sTfR1, or the sTfR1-Ferritin Index. Further studies are recommended to focus on the role of this SNP in IDA
BACKGROUND
Metabolically-dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and is strongly influenced by genetic susceptibility. Among the identified genetic variants, the patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 (I148M) polymorphism has been consistently associated with hepatic steatosis and disease progression. However, previous meta-analyses included fewer studies, limited ethnic diversity, and insufficient investigation of between-study heterogeneity. This study aimed to comprehensively evaluate the association between the PNPLA3 rs738409 polymorphism and MASLD susceptibility.
METHODS
A systematic literature search was conducted in PubMed, Embase, Scopus, Web of Science, and Google Scholar to identify eligible case-control studies published between 2015 and 2025. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated under allelic, dominant, homozygous, heterozygous, and combined genotype models using random-effects meta-analysis. Between-study heterogeneity was assessed using the I² statistic, and ethnicity-based subgroup analyses were performed to investigate potential sources of heterogeneity.
RESULTS
Forty-one studies comprising 9,064 patients with MASLD and 10,894 controls were included. The G allele was significantly associated with increased susceptibility to MASLD (OR = 1.70, 95% CI: 1.49-1.93). Individuals carrying the GG genotype had approximately a twofold higher risk of MASLD (OR = 2.00, 95% CI: 1.65-2.42), whereas the CC genotype showed a protective association (OR = 0.51, 95% CI: 0.44-0.59). Significant associations were also observed for the CG genotype (OR = 1.22, 95% CI: 1.08-1.38) and the dominant model (CG + GG vs. CC) (OR = 2.64, 95% CI: 1.86-3.75). Although substantial between-study heterogeneity was observed (I² = 66%-96%), ethnicity-based subgroup analyses explained part of the variability while demonstrating consistent associations across major ethnic populations.
CONCLUSIONS
This updated meta-analysis confirms that the PNPLA3 rs738409 (I148M) polymorphism is a major genetic susceptibility factor for MASLD across diverse populations. Although ethnicity contributes to between-study heterogeneity, the association remains robust across populations. These findings support the incorporation of PNPLA3 into multifactorial risk assessment models and provide an updated evidence base for future precision medicine approaches in MASLD.
Muteia Hamood, M. A. Al-Salehi, Ali Hussein et al.· BMC Gastroenterology· 0 citations
BACKGROUND
Gestational diabetes mellitus (GDM) has a high global prevalence and arises from complex interactions between genetic predisposition and environmental factors. GDM is associated with metabolic disturbances and chronic low-grade inflammation, both of which contribute to its pathogenesis. This study aimed to investigate the association between GDM and 135 single-nucleotide polymorphisms (SNPs) across 20 genes related to metabolic traits.
METHODS
In this case-control study, 152 pregnant women with GDM and 684 pregnant women with normal glucose tolerance (NGT) who underwent antenatal examination at Siriraj Hospital, Bangkok, were enrolled. Clinical data and blood samples were collected from all participants. Genomic DNA was isolated and subjected to whole-genome sequencing using the DNBSEQ-T7RS high-throughput sequencing platform. Genotype analyses were performed using R software, and haplotype analyses were conducted using the online SNPStats software.
RESULTS
After adjusting for maternal age and pre-pregnancy body mass index, polymorphisms in TCF7L2 (rs34872471, rs7901695, rs4506565, rs7903146, rs12243326, and rs12255372), NEDD1 (rs10431408, rs11830756, rs249579, rs249585, and rs4762339), CMIP (rs2306115 and rs201681534), CDKAL1 (rs4710942), GCKR (rs2293572 and rs2293571), and GCK (rs5883890) were significantly associated with the risk of GDM. Haplotype analysis demonstrated that the TCF7L2 rs12243326-rs12255372 CA haplotype was associated with a decreased risk of GDM (OR = 0.44, 95% CI: 0.23-0.81), while the NEDD1 rs249579-rs249585-rs4762339 GGT haplotype was associated with an increased risk of GDM (OR = 1.40, 95% CI: 1.08-1.82).
CONCLUSIONS
These findings suggest that genetic variations in TCF7L2, NEDD1, CMIP, CDKAL1, GCK, and GCKR contribute to GDM susceptibility in the Thai population.
Sarocha Suthon, Wachirawit Angkatavanich, S. Mohamud et al.· Annals medicus· 0 citations
OLR1 rs11053646 SNP does not appear to be associated with T2D risk in Saudi adults, and small sample size may have limited statistical power to detect potential associations.
V. Vennu· Endocrine, Metabolic & Immun...· 0 citations
Tuberculosis (TB) remains a major infectious disease burden, and inter-individual heterogeneity in progression from exposure to active disease suggests contributions from host genetic factors. SLC11A1 (formerly NRAMP1) encodes a phagosomal divalent cation transporter implicated in macrophage-mediated antimicrobial defense; the non-synonymous rs17235409 polymorphism (D543N) has been evaluated in multiple populations with inconsistent results. We conducted a retrospective matched case–control study in Qiandongnan, Guizhou Province, China, including 50 patients diagnosed with TB (2022–2023) and 50 healthy controls frequency-matched by ethnicity and selected demographics. Participants were drawn from Miao, Dong, and other minority groups. Among TB cases, the frequencies of the GG, GA, and AA genotypes were 80.0%, 20.0%, and 0%, respectively, compared with 74.0%, 18.0%, and 8.0% among controls. The overall genotype distribution did not differ significantly between the 2 groups (P = .124). Under the dominant model, no significant association was observed between rs17235409 and TB susceptibility (OR = 0.71, 95% CI: 0.28–1.82; P = .635). Allelic analysis showed that the frequency of the A allele was lower in cases than in controls (10.0% vs 17.0%), but this difference was not statistically significant (OR = 0.54, 95% CI: 0.24–1.25; P = .214). Ethnicity-stratified analyses similarly showed no statistically detectable associations in Miao, Dong, or other groups. The minor allele frequency was 0.095, lower than the Han Chinese reference from 1000 Genomes. In this pilot study of multi-ethnic populations from southwestern China, no statistically significant association was identified between the SLC11A1 rs17235409 polymorphism and tuberculosis susceptibility. Although the A allele appeared less frequent among cases, the limited sample size and statistical power preclude definitive conclusions regarding modest or ethnic-specific effects. These findings provide preliminary genetic data from underrepresented ethnic minority populations and warrant validation in larger multicenter studies.
Objectives: To determine the association of polymorphism rs10741657 in the CYP2R1 gene with vitamin D deficiency in apparently healthy subjects.
Method: The prospective, case-control study was conducted from June 2023 to January 2024 at the CREAM Lab of Army Medical College, Rawalpindi, and comprised vitamin D-deficient cases in group A and healthy controls in group B. Genotyping of rs10741657 polymorphism in the CYP2R1 gene was performed using allele-specific polymerase chain reaction (AS-PCR). Genotypic and allelic frequencies, Hardy–Weinberg equilibrium, and genetic inheritance models were analysed using SNPStats, a web-based statistical software for genetic association studies.
Results: Of the 300 subjects with a mean age of 43.56 ± 15.26 years, 150 (50%) were in group A, comprising 91 (61%) females and 59 (39%) males, with a mean age of 44.49 ± 15.12 years. There were 150 (50%) controls in group B, including 83 (55%) males and 67 (45%) females, with a mean age of 42.63 ± 15.40 years. The genotypic frequencies in group A were A/A 45(30%), A/C 101(67.34%), C/C 4(2.66%). The corresponding values in group B were 39(26%), 110(73.34%) and 1(0.66%). The allele frequency of A was 191 (64%) in vitamin D-deficient cases and 188 (63%) in healthy controls (p = 0.8775), while the C allele frequency was 109 (36%) in cases and 112 (37%) in controls (p = 0.8401). The genotype frequencies in cases were A/A 45 (30%), A/C 101 (67%), and C/C 4 (2.67%), compared to A/A 39 (26%), A/C 110 (73%), and C/C 1 (0.67%) in controls, with no statistically significant difference observed between the groups (p > 0.05). The inheritance genetic models suggested no association with vitamin D deficiency (p>0.05); codominant model – A/C odds ratio 0.70 (95% confidence interval: 0.45-1.23), C/C odds ratio 4.00 (95% confidence interval: 0.45-36.96); dominant model odds ratio 0.80 (95% confidence interval: 0.49-1.35); recessive model odds ratio 4.00 (95% confidence interval: 0.45-36.96); and overdominant model odds ratio 0.70 (95% confidence interval: 0.45-1.23).
Conclusion: The A allele was found to be the most common variant of rs10741657 in both the groups. The rs10741657 polymorphism was not a risk for the susceptibility to vitamin D deficiency. No correlation of genotype with serum vitamin D levels was noted.
Key Words: Allele-specific polymerase chain reaction, Single nucleotide polymorphism, Calcitriol, 25 Hydroxylase, Vitamin D binding protein.
Abdur Rauf, Asifa Majeed· JOURNAL OF PAKISTAN MEDICAL...· 0 citations
