Type 2 diabetes mellitus (T2DM) is a chronic and metabolic disorder that affects the adult population. Chemokines are proinflammatory cytokines that play a role in the development of chronic diseases such as obesity, gestational diabetes, and T2DM. The C-C Motif Chemokine Ligand 5 (CCL5) gene plays a role in antiviral immunity, tumor development, obesity, impaired glucose tolerance, and T2DM. This study aimed to investigate the genetic role of the rs2107538 variant in the CCL5 gene in Saudi patients with T2DM. Sixty subjects with T2DM patients and 60 healthy controls participated in this prospective case-control study. Prior to Sanger sequencing, genomic DNA was extracted and amplified with Polymerase chain reaction (PCR), after which the PCR products were purified. The collected data were used to conduct various statistical analyses to determine the relationship between T2DM and control subjects. The findings of the current study revealed a positive association for most parameters between T2DM and control subjects (p < 0.05). The frequency of genotypes (p = 0.002, AA vs.GG: p = 0.008, GA + AA vs. GG: p = 0.0002) and alleles (A vs. G: p = 0.0007) revealed a strong risk association. Multiple logistic regression with individual effects revealed a link between SBP and HDLc levels (p = 0.03). In patients with T2DM, waist (p = 0.001), TG (p = 0.0007), and LDLc (p = 0.0004) levels were all associated with the ANOVA. Finally, the rs2107538 variant was linked to an increased risk of T2DM in the Saudi Population. The GA and AA genotypes were strongly connected to the T2DM subjects. In order to rule out disease-causing variants in the global population, future research should use a large sample size.

Polycystic ovary syndrome (PCOS) is an ovarian health condition as well as a long-term endocrine dysfunction that affects reproductive-aged women. Toll-like receptor 2 (TLR2) gene was linked to PCOS and chronic inflammation, and the prevalence of obesity was rising in Saudi women. Previous studies on rs5743708 polymorphism were documented in the obesity as well as in PCOS women. In this study, we investigated the molecular role of rs5743708 polymorphism in TLR2 gene among Saudi women diagnosed with PCOS using the Rotterdam criteria. Blood samples were collected from 220 Saudi women in this hospital-based case-control study; 110 were PCOS women and remaining 110 were non-PCOS (control women). Biochemical analysis was performed on serum samples, and molecular analysis was performed on EDTA blood. Genotyping for rs5743708 polymorphism was performed with polymerase chain reaction-restriction fragment length polymorphism analysis. In both groups, clinical data was calculated using t-test, which revealed both positive (p < 0.05) and negative (p > 0.05) associations. HWE analysis supported the rs5743708 polymorphism (p < 0.05). In the rs5743708 polymorphism, none of the genotypes, genetic models, or allele frequencies were found to be associated with PCOS and non-PCOS women. However, both ANOVA and regression analyses revealed a positive relationship in PCOS with weight and BMI (p < 0.0001). The rs5743708 polymorphism was not associated to PCOS in Saudi women. One of the predictions could be that 42.7% of PCOS and 73.6% of non-PCOS women were obese, and the rs5743708 polymorphism has been linked to both obesity and PCOS in the previous studies. This study suggests screening for additional polymorphisms with a large sample size.

Female infertility (FI) is a global health issue. Polycystic ovary syndrome (PCOS) is a common cause of FI. The renalase gene (RNLS) is associated with FI and other human diseases. Based on the documented missense variants, rs6166 and rs2296545 single-nucleotide polymorphisms (SNPs) were not identified in Saudi women with FI and PCOS. This study aimed to investigate the molecular role of the two SNPs in Saudi women with FI and PCOS. In this cross-sectional study, 96 healthy controls, 96 women with FI, and 96 women with PCOS were recruited. DNA was isolated, and polymerase chain reactions and Sanger sequencing analysis were performed using rs6166 and rs2296545 SNPs. The data obtained from the three groups were used to perform statistical analyses based on genotype, allele frequencies, regression models, and ANOVA analysis. Both rs6166 and rs2296545 had no role in FI or PCOS in Saudi women. A predicted reason for non-association in Saudi women could be the role of elderly women in the controls compared with women with FI and PCOS. Moreover, age, weight, and body mass index were higher in the control group than the FI and PCOS groups. In conclusion, rs6166 and rs2296545 SNPs were not associated with FI or PCOS in Saudi women.

The traditional definition of gestational diabetes mellitus (GDM) is the leading cause of carbohydrate intolerance in hyperglycemia of varying severity, with onset or initial detection during pregnancy. Previous studies have reported a relationship among obesity, adiponectin (ADIPOQ), and diabetes in Saudi Arabia. ADIPOQ is an adipokine that is produced and secreted by adipose tissue involved in the regulation of carbohydrate and fatty acid metabolism. This study investigated the molecular association between rs1501299, rs17846866, and rs2241766 single-nucleotide polymorphisms (SNPs) in ADIPOQ and GDM in Saudi Arabia. Patients with GDM and control patients were selected, and serum and molecular analyses were performed. Statistical analyses were performed on clinical data, Hardy Weinberg Equilibrium, genotype and allele frequencies, multiple logistic regression, ANOVA, haplotype, linkage disequilibrium, as well as MDR and GMDR analyses. The clinical data showed significant differences in various parameters between the GDM and non-GDM groups (p < 0.05). In GDM women with alleles, genotypes, and different genetic models, the rs1501299 and rs2241766 SNPs showed a strong association (p < 0.05). Multiple logistic regression analysis revealed a negative correlation (p > 0.05). This study concluded that rs1501299 and rs2241766 SNPs were strongly associated with GDM in women in Saudi Arabia.

Polycystic ovary syndrome is a complex disorder defined by the Rotterdam criteria. Insulin resistance is a common factor for the development of type 2 diabetes mellitus among women with PCOS. The SLC2A2 gene has been identified as a T2DM gene by genome-wide association studies in the rs8192675 SNP. This study aimed to investigate the rs8192675 SNP in women diagnosed with PCOS on a molecular level and further for T2DM development in the Saudi women. In this case-control study, 100 PCOS women and 100 healthy controls were selected. Among 100 PCOS women, 28 women showed T2DM development. Genotyping for rs8192675 SNP was performed by PCR-RFLP analysis. Additionally, Sanger sequencing was performed to validate the RFLP analysis. The obtained data were used for a statistical analysis for the genotype and allele frequencies, logistic regression, and ANOVA analysis. The clinical data confirmed the positive association between FBG, FI, FSH, TT, TC, HDLc, LDLc, and family histories (p < 0.05). HWE analysis was associated in both the PCOS cases and the control individuals. Genotype and allele frequencies were associated in PCOS women and strongly associated with women with PCOS who developed T2DM (p < 0.05). No association was found in the logistic regression model or ANOVA analysis studied in women with PCOS (p > 0.05). A strong association was observed between the rs8192675 SNP and women with PCOS who developed T2DM using ANOVA analysis (p < 0.05). This study confirms that the rs8192675 SNP is associated with women with PCOS and strongly associated with women with PCOS with developed T2DM in Saudi Arabia.

Purpose: Aging is characterized by the gradual physiological changes and alterations that accumulate over time in the human body. The combination of obesity and ageing can lead to an increased risk of serious health issues or death. Single nucleotide variants (SNVs) in the Klotho gene were commonly studied, including that in type 2 diabetes mellitus (T2DM). Aim: The aim of this study is to examine the possible effect of SNVs in Klotho on the obese population in Saudi Arabia using middle-aged participants with and without T2DM. Methods: This study consists of 100 controls and 100 obesity patients, in which 50 had T2DM and the remaining 50 were obese without T2DM. Genotyping was performed with PCR, and Sanger sequencing analysis was used to validate the molecular association. Results: In this study, rs1207568 (p = 0.001– 0.003) and rs9527025 (p = 0.001– 0.00004) SNVs were associated with obesity cases. However, none of the genotypes or allele frequencies showed a positive association with the rs564481 SNV (p = 0.344– 0.881). The multiple linear regression model showed that waist and hip were associated (p = 0.01– 0.02). ANOVA analysis showed age (p = 0.04), hip (p = 0.002), SBP, and TC (p = 0.02) were associated. Finally, SNV (rs1207568 and rs95270250) and obesity (p < 0.001) associations were confirmed through gene multifactor dimensionality reduction analysis with gene–gene interaction, dendrogram, and graphical depletion method. Conclusion: This study concludes that rs1207568 and rs9527025 SNVs are associated with obesity in the Saudi population. Additional genetical statistics showed significant association between dependent and independent variables. SNVs in Klotho play a role in the Saudi population’s susceptibility to obesity.