BACKGROUND:Obesity is a complex condition caused by environmental and hereditary factors. Single nucleotide polymorphisms (SNPs) in the FTO (rs9939609) and melanocortin-4-receptor (MC4R) (rs17782313) genes have been strongly linked to an increased risk of obesity. This study sought to determine the relationship between these polymorphisms and their combined effects on the risk of obesity in Quetta, Pakistan. METHODS:A total of 250 individuals (150 obese and 100 non-obese) aged 18-65 were recruited from Sardar Bahadur Khan Women's University, Bolan Medical Complex Hospital, and the overall Quetta population. Anthropometric measurements, lifestyle characteristics, and demographic information were gathered using standardized questionnaires. The fat mass and obesity associated FTO rs9939609 and Melanocortin-4-receptor MC4R rs17782313 genes were genotyped using the amplification refractory mutation system polymerase chain reaction method. RESULTS:Both SNPs were associated with obesity across multiple genetic models. For FTO rs9939609, the risk variant significantly increased obesity susceptibility under co-dominant (odds ratio [OR] = 4.13, p = 0.010), recessive (OR = 3.44, p = 0.011), and dominant (OR = 1.91, p = 0.013) models; Similarly, the MC4R rs17782313 variant demonstrated robust association in co-dominant (OR = 3.33 and 3.64, p = 0.009), recessive (OR = 3.37, p = 0.002), and dominant models (OR = 1.88, p = 0.037). Both SNPs deviated from Hardy-Weinberg equilibrium in the obese group, indicating possible selection pressure; risk genotypes were also significantly associated with higher body mass index, weight, and waist-hip ratio (p < 0.05). Furthermore, combined genotype analysis revealed that the MC4R/FTO variant combination TT/AA (OR = 0.19, p = 0.006) and CC/AT (OR = 0.12, p = 0.002) were significantly predictive of obesity status compared to the wild-type baseline. CONCLUSION:This study shows a clear correlation between the higher incidence of obesity in Quetta, Pakistan, and the FTO rs9939609 and MC4R rs17782313 polymorphisms. These results of the study play an important role in genetic screening for the evaluation of obesity risk and play an essential role in research related to the role of genetic variables in public health initiatives aimed at preventing obesity.
PURPOSE:To report a Chinese family with lattice corneal dystrophy (LCD) caused by the TGFBI p.H626R mutation and summarize its clinical and genetic characteristics through a literature review. METHODS:A three-generation Chinese family with LCD was investigated through detailed ophthalmic examination. Whole-exome sequencing followed by Sanger sequencing was performed to identify candidate variants. Bioinformatics tools were used to evaluate pathogenicity. Previously reported cases of H626R-associated LCD were reviewed. RESULTS:A heterozygous TGFBI mutation (c.1877A>G; p.His626Arg) was identified in affected individuals. All patients underwent penetrating keratoplasty at advanced stages, with improved postoperative visual acuity. A pooled analysis of 109 patients from at least 12 countries indicated that H626R-associated LCD is characterized by recurrent corneal erosions, asymmetrical progression, and thick lattice lines extending toward the corneal periphery. CONCLUSIONS:The TGFBI p.H626R mutation is associated with a distinct LCD phenotype and contributes to disease progression. Most affected individuals underwent penetrating keratoplasty at the advanced stage of the disease to restore visual acuity.
Background: Biotinidase is an enzyme recycling endogenous biotin by hydrolyzing ε- N -biotinyl lysine (biocytin) to lysine and biotin. Biotin acts as a coenzyme in various carboxylation reactions. Biotinidase deficiency is rare, with an incidence of 1 per 112,271 individuals. Objectives: Genetic characterization of a 4-month-old boy born out of a consanguineous marriage presented with cutaneous manifestations, alopecia, developmental delay, hypotonia with absent neck holding, respiratory problems, and biotinidase deficiency. Methods: Biochemical characterization was performed using tandem mass spectrometry and immunofluorescence enzyme assays. Pathogenic genetic variant was identified by Sanger sequencing of the BTD (biotinidase) gene in a patient and his parents. Results: Biochemical characterization indicated elevated methylmalonylcarnitine/hydroxyisovalerylcarnitine and decreased biotinidase, citrulline, glycine, and ornithine levels, suggesting a profound biotinidase deficiency. Sequencing of BTD gene indicates the presence of a 7-bp deletion and a 3-bp insertion (98-104del7ins3) in a homozygous state, resulting in a change of amino acid from cystine to phenylalanine at the 33rd position, causing a frameshift and premature amino acid termination at the 68th position. Conclusions: A 7-bp deletion and a 3-bp insertion (98-104del7ins3) homozygous variation in the BTD gene segregating in a homozygous recessive manner in the family, causing truncated, nonfunctional biotinidase deficiency in the proband. This is a recurrent mutation and has the potential to be used as a biomarker for screening patients with biotinidase deficiency.
BACKGROUND:Because the IL-17/IL-17 receptor (IL-17R) axis is involved in lung inflammation and genetic variants, such as single nucleotide polymorphisms (SNPs), can affect its function, this study examined the associations between IL-17/IL-17R gene SNPs, serum IL-17A levels, and community-acquired pneumonia (CAP) in Iranian children. METHODS:A total of 266 subjects were enrolled in this study, comprising 126 children with CAP and 140 healthy controls. Genetic variants in the IL-17 and IL-17R genes were characterized by allele-specific PCR and PCR restriction fragment length polymorphism, respectively. Concurrently, serum IL-17A concentrations were measured by enzyme-linked immunosorbent assay. RESULTS:Serum IL-17A levels were significantly higher in patients than in controls (295.8 ± 138.5 pg/mL vs. 40.6 ± 35.3 pg/mL, respectively; p = 0.001). Although the allele and genotype frequencies of IL-17 rs4711998 and IL-17 rs3748067 showed no significant association with CAP, the AA genotype and A allele of IL-17R rs4819554 were significantly more frequent in the patient group. Correlation analysis found no significant association between IL-17 genotypes and serum IL-17A levels. However, a significant positive correlation was observed between IL-17A levels and fever (p = 0.001). CONCLUSION:The upregulation of IL-17A in patient sera and its correlation with fever support a role for IL-17A in the pathogenesis of CAP. Furthermore, the A allele and AA genotype of IL-17R rs4819554 were identified as potential risk factors for CAP in Iranian children. The lack of a significant association between IL-17 gene variants and serum IL-17A levels may be attributable to the complex regulatory network governing IL-17 production.
Background: Glutathione-S-transferases (GSTs) play an important role in the detoxification and neutralization of oxidative stress products and xenobiotic compounds. Due to genetic polymorphisms in GST genes, GSTs partially or completely lose enzymatic activity, which may increase susceptibility to cardiovascular diseases. The objective of this study was to investigate hitherto unknown GSTM1 and GSTT1 null genotype frequencies in patients with coronary artery disease (CAD) and their potential association with CAD in the Bangladeshi population. Materials and Methods: This study included 85 patients with CAD and 56 healthy control subjects confirmed by angiogram. Clinical parameters including triglyceride (TG), cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein levels were also evaluated. Genotypes of the GSTM1 and GSTT1 genes were identified using polymerase chain reaction followed by 1.5% (W/V) agarose gel electrophoresis with subsequent detection on a UV transilluminator. Results: There were significant differences in the null genotype distribution of GSTM1 and GSTT1 alleles between controls and patients with CAD. A significant association of the null genotype with CAD susceptibility ( p < 0.05) was also observed. The combination of GSTM1 and GSTT1 null genes potentially increases the risk of CAD (odds ratio = 6.208; 95% confidence interval; p < 0.05). TG, LDL, and serum cholesterol levels were higher in patients with CAD ( p < 0.05). GSTM1 and GSTT1 null genetic variations may be associated with increased susceptibility to CAD in the Bangladeshi population. Conclusion: These findings suggest a potential association between GST gene polymorphisms and CAD susceptibility; however, larger studies are required to provide more robust and generalizable evidence in the Bangladeshi population.
