The role of FTO variant rs1421085 in the relationship with obesity: a systematic review and meta-analysis.

PURPOSE: Fat mass and obesity-associated (FTO) is considered the first locus associated with adiposity, a concerning health problem worldwide. Many studies have evaluated the relationship between the FTO variants and obesity susceptibility. While the strong association of FTO rs1421085 with the risk of obesity across populations was reported in different studies, some researchers found a lack of association of this variant with adiposity. This systematic review and meta-analysis aimed to assess the association between obesity and rs1421085 polymorphism. METHODS: We systematically searched PubMed, Scopus, and Google Scholar up to June 2022 to find pertinent studies. To further assess this issue, we surveyed the probable association of rs1421085 with obesity development among Iranian adults using the logistic regression analysis, and the obtained results were used for doing meta-analysis. After selection, nine eligible studies were included in the meta-analysis through the random- and fixed-effect models to determine the combined odds ratios (OR) and 95% confidence intervals (CI). RESULTS: According to our meta-analysis conducted on 5169 obese and 7772 non-obese individuals using different genetic models, including recessive, dominant, over-dominant, and additive, rs1421085 could positively increase the risk of obesity under all tested genetic models. Also, we detected a high to moderate level of heterogeneity among different studies under various genetic models. CONCLUSION: This meta-analysis further verified the positive association of FTO rs1421085 with the risk of developing obesity. STUDY REGISTRATION: This study is registered as PROSPERO CRD42021220092. LEVEL OF EVIDENCE: Level I, systematic reviews and meta-analyses.

Comparing newly developed SNP barcode panels with microsatellites to explore population genetics of malaria parasites in the Peruvian Amazon.

Malaria molecular surveillance (MMS) can provide insights into transmission dynamics, guiding national control/elimination programs. Considering the genetic differences among parasites from different areas in the Peruvian Amazon, we previously designed SNP barcode panels for Plasmodium vivax (Pv) and P. falciparum (Pf), integrated into AmpliSeq assays, to provide population genetics estimates of malaria parasites. These AmpliSeq assays are ideal for MMS: multiplexing different traits of interest, applicable to many use cases, and high throughput for large numbers of samples. The present study compares the genetic resolution of the SNP barcode panels in the AmpliSeq assays with widely used microsatellite (MS) panels to investigate Amazonian malaria parasites. Malaria samples collected in remote areas of the Peruvian Amazon (51 Pv & 80 Pf samples) were characterized using the Ampliseq assays and MS. Population genetics estimates (complexity of infection, genetic diversity and differentiation, and population structure) were compared using the SNP barcodes (Pv: 40 SNPs & Pf: 28 SNPs) and MS panels (Pv: 16 MS & Pf: 7 MS). The genetic diversity of Pv (expected heterozygosity, He ) was similar across the subpopulations for both makers: He MS = 0.68 - 0.78 (p = 0.23) and He SNP = 0.36 - 0.38 (p = 0.80). Pairwise genetic differentiation (fixation index, F ST ) was also comparable: F ST-MS = 0.04 - 0.14 and F ST-SNP = 0.03 - 0.12 (p = 0.34 - 0.85). No geographic clustering was observed with any panel. In addition, Pf genetic diversity trends ( He MS = 0 - 0.48 p = 0.03 - 1; He SNP = 0 - 0.09, p = 0.03 - 1) and pairwise F ST comparisons (F ST-MS = 0.14 - 0.65, F ST-SNP = 0.19 - 0.61, p = 0.24 - 0.83) were concordant between the panels. Similar population structure clustering was observed with both SNP and MS, highlighting one Pf subpopulation in an indigenous community. The SNP barcodes in the Pv AmpliSeq v2 Peru and Pf AmpliSeq v1 Peru assays offer comparable results to MS panels when investigating population genetics in Pv and Pv populations. Therefore, the AmpliSeq assays can efficiently characterize malaria transmission dynamics and population structure and support malaria elimination efforts in Peru.

Estimating the cure proportion of colorectal cancer and related factors after surgery in patients using parametric cure models.

AIM: This study aimed to estimate the cure proportion and effects of related factors on colorectal cancer in Iranian patients after surgery. BACKGROUND: Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the fourth leading cause of cancer death. The relative survival of CRC varies worldwide given the quality of care, including surgical techniques. METHODS: This retrospective cohort study was conducted on 490 patients, aged 20-94 years, with colorectal cancer. All the colorectal cancer patients undergoing surgery in Faghihi hospital, Shiraz University of Medical Sciences were prospectively followed-up for 8 years from 2008 to March 8, 2016. We used parametric cure model (mixture and non-mixture) to estimate the cure proportion and the adjusted hazard ration (HR) for colorectal cancer mortality after surgery. Data were analyzed by the "flexsurvcure" package in R software (version 3.4.2). RESULTS: The median age of patients was 57.5 (interquartile range =18) years. Specifically, 56.33% of the patients were male. The median time of follow-up in patients was 618 days. The cumulative survival proportion varied from 0.90 to 0.49 which indicated a reduction followed by a flat line in the probability of survival by sex. The flexible survival for adjusted cure proportion (%) was 68.3. Only obesity was associated with a decreased risk of mortality (HR=0.34; 95% CI: 0.12-0.97). CONCLUSION: The overall eight-year survival proportion and adjusted cure proportion for CRC were 49% and 68.3%, respectively. Knowing the cure proportion and its related factors in patients with CRC, better services can be provided. Thus, early detection and screening strategies are required to reduce mortality and increase survival of patients.