Rs9939609 Polymorphism Research Articles

The melatonin receptor gene polymorphism rs10830963 is not associated with significant differences in sleep patterns and biorhythms.

The melatonin receptor gene polymorphism rs10830963 is not associated with significant differences in sleep patterns and biorhythms.

Abstract #1183142: TCF7L2 Genetic Variation and the Acute Glycaemic Response to Metformin in Patients With Type 2 Diabetes

TCF7L2 may affect fasting and postprandial hyperglycaemia in carriers of the rs7903146 polymorphism due to its crucial role in hepatic glucose production. Metformin functions by reducing hepatic glucose production while simultaneously increasing peripheral glucose uptake. Thus the intensity of response under application of metformin may depend on the presence of TCF7L2 gene polymorphism. The aim was to analyze the association between rs7903146 polymorphism of the TCF7L2 gene and acute metformin glycaemic response in patient with newly diagnosed type 2 diabetes (T2D) measured by continuous glucose monitoring (CGM).

152P Prognostic impact of serum vascular endothelial growth factor and VEGF gene polymorphism (rs2010963) in breast cancer patients

Vascular Endothelial Growth Factor (VEGF) mediates breast carcinogenesis, several studies shown that VEGF is associated with increased breast cancer risk however its prognostic significance and expression in different molecular subtypes remain unclear. The current study aimed to evaluate the diagnostic and prognostic role of serum VEGF and VEGF rs2010963 polymorphism in Egyptian women with breast cancer.

Sociodemographic and genetic determinants of nonalcoholic fatty liver disease in type 2 diabetes mellitus patients

BackgroundNonalcoholic fatty liver disease (NAFLD) showed significant association with PNPLA3 rs738409 polymorphism in unrelated individuals. However, it is still unknown whether the relationship of NAFLD with PNPLA3 variant exists or not among subjects with type 2 diabetes mellitus (T2DM). Therefore, the study aimed to evaluate sociodemographic and genetic determinants of NAFLD in type 2 diabetics. MethodsThe cross-sectional analytical study was conducted at the Department of Molecular Biology, Virtual University of Pakistan, Lahore, Pakistan, during 2019–2020. A total of 153 known cases of T2DM were enrolled using convenience sampling. After excluding patients (n = 24) with HCV, alcoholism, or missing information, data from 129 eligible diabetics with and without NAFLD were analyzed using SPSS. Odds ratios using crosstabs and adjusted odds ratios using binary and multinomial logistic regression were calculated to measure the risk of NAFLD. ResultsAdults 18–35 years were 7.0%, 36–55 years were 64.3%, ≥ 56 years were 28.7%, and females were 66.7%. A total of 41.1% of patients had obesity, 52.7% had NAFLD, and 29.05% carried mutant G allele of rs738409 polymorphism. Among overall diabetics, NAFLD showed association with female (OR = 2.998, p = 0.007), illiterate (OR = 3.067, p = 0.005), and obese (OR = 2.211, p = 0.046) but not with PNPLA3 genotype under any model (all p = > 0.05). Among obese diabetics, NAFLD showed association with female (AOR = 4.010, p = 0.029), illiterate (AOR = 3.506, p = 0.037), GG + CG/CC (AOR = 3.303, p = 0.033), and GG/CG + CC (AOR = 4.547, p = 0.034) using binary regression and with female (AOR = 3.411, p = 0.051), illiterate (AOR = 3.323, p = 0.048), GG + CG/CC (AOR = 3.270, p = 0.029), and GG/CG + CC (AOR = 4.534, p = 0.024) using multinomial regression. ConclusionsNAFLD and obesity were the most common comorbid diseases of T2DM. Gender female, being illiterate, and PNPLA3 rs738409 polymorphism were significant risk factors of NAFLD among obese diabetic patients.

Influence of Type 2 Diabetes in the Association of PNPLA3 rs738409 and TM6SF2 rs58542926 Polymorphisms in NASH Advanced Liver Fibrosis.

Nonalcoholic steatohepatitis (NASH) is a leading cause of cirrhosis in western countries. Insulin resistance (IR), type 2 diabetes (T2D), and the polymorphisms patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 and transmembrane 6 superfamily member 2 (TM6SF2) rs58542926 are independent risk factors of NASH. Nevertheless, little is known about the interaction between IR and T2D with these polymorphisms in the pathogenesis of NASH and the development of advanced fibrosis. Thus, our study aimed to investigate this relationship. This is a cross-sectional study including NASH patients diagnosed by liver biopsy, at the Vall d’Hebron University Hospital. A total of 140 patients were included (93 T2D, 47 non-T2D). T2D (OR = 4.67; 95%CI 2.13–10.20; p < 0.001), PNPLA3 rs738409 and TM6SF2 rs58542926 polymorphisms (OR = 3.94; 95%CI 1.63–9.54; p = 0.002) were independently related with advanced liver fibrosis. T2D increased the risk of advance fibrosis on top of the two polymorphisms (OR = 14.69; 95%CI 3.03–77.35; p = 0.001 for PNPLA3 rs738409 and OR = 11.45; 95%CI 3.16–41.55; p < 0.001 for TM6SF2 rs58542926). In non-T2D patients, the IR (HOMA-IR ≥ 5.2, OR = 14.33; 95%CI 2.14–18.66; p = 0.014) increased the risk of advanced fibrosis when the polymorphisms were present (OR = 19.04; 95%CI 1.71–650.84; p = 0.042). The T2D and IR status increase the risk of advanced fibrosis in patients with NASH carrying the PNPLA3 rs738409 and/or TM6SF2 rs58542926 polymorphisms, respectively.

Association of rs9939609 polymorphism in the FTO gene with features of androgen status in men

The purpose of the study was to investigate the association of carriage of rs9939609 polymorphism in the FTO gene with features of androgen status in men.Material and methods. The observational one-stage examination of 139 male patients aged 22 to 69 years, admitted to a therapeutic hospital in a planned manner has been carried out in the Clinic of the Federal Research Center for Fundamental and Translational Medicine in the period 2020–2021. All fasting men in the morning (8:00–8:30) were carried out of an anthropometric examination to determine physical development, sampling of venous blood from the cubital vein to assess the hormonal parameters of androgen status, and taking a sample of the buccal epithelium for molecular genetic research. Based on the carriage of the rs9939609 (T&gt;A) polymorphism of the FTO gene, the following groups (G) of patients were distinguished: G1 – wild-type homozygotes (WT/WT), G2 – heterozygotes (WT/A), G3 – homozygotes for the mutant allele (A/A).Results and discussion. The statistically significant differences were found in the levels of total testosterone between G1 and G3 (11.6 vs 14.5 nmol/L, p = 0.010), as well as free testosterone in G1 compared to G2 (0.233 vs 0.287 nmol/L, p = 0.012) and G3 (0.233 vs 0.321 nmol/L, p = 0.002) when analyzing the clinical-anthropometric and hormonal features of the androgen status of the examined male patients in the selected groups. Assessment of the association revealed statistically significant positive correlations between the carriage of the mutant allele and the levels of total (r = 0.247; p = 0.013) and free (r = 0.296; p = 0.003) testosterone, and negative - with the frequency of androgen deficiency according to the free testosterone criteria (r = –0.240; p = 0.016).Conclusions. It has been shown that the carriage of the A/A genotype of rs9939609 polymorphism of the FTO gene is associated with an increase in the levels of total and free testosterone, that indicates a protective effect against the development of androgen deficiency in men. The obtained results suggest that this effect is due to the epigenetic effect of the FTO gene protein product on the expression of other genes involved in the synthesis of androgens in the gonads, but also in the adrenal cortex since no association of the carriage of the rs9939609 polymorphism of the FTO gene with the DHEA-C level was found.

Association of rs7903146 TCF7L2, rs1042714 ADRB2 with the changes in body fat mass in different types of therapy of early carbohydrate metabolism disorders

BACKGROUND: Depending on the polymorphism of genes that that are involved in metabolism, the response of patients to different types of therapy may differ. Despite the potential effect of rs7903146 TCF7L2 and rs1042712 ADRB2 on changes in body composition in different types of therapy of early carbohydrate metabolism disorders, these associations haven’t been studied yet. AIM: To study the influence of rs7903146 TCF7L2, rs1042714 ADRB2 on changes in body fat composition in different types of therapy of early carbohydrate metabolism disorders.MATERIALS AND METHODS: The study involved patients with overweight or obesity and risk factors for Type 2 Diabetes development. All patients underwent genotyping with the real-time polymerase chain reaction, oral glucose tolerance test and bioimpedancemetry. Further, the patients were divided into two groups. First group kept a diet with the exclusion of simple and limitation of complex carbohydrates and fats. Second group took metformin in addition to the diet. Three months after bioimpedancemetry was performed again.RESULTS: The research involved 73 patients (the mean age 48±12 y.o., the mean BMI 34,27±6,18 kg/m2 ). The diet therapy group consisted of 47 people. Other 26 patients took metformin in addition to the diet. In group of diet, T allele carriers of rs7903146 TCF7L2 were characterized with more decrease in fat mass compared with CC homozygotes (- 7.90 ± 9.46% vs. -1.54 ± 8.98%, p = 0.027). CC genotype carriers of rs7903146 TCF7L2 in group of metformin and the diet had a tendency for more decrease in hip circumference compared with T allele carriers (-4.95 ± 3.34% vs. — 2.5 ± 2.96%, p = 0.064). Carriers of C allele in homozygous state of rs1042714 ADRB2, who took metformin with the diet, demonstrated more decrease in hip circumference (- 5.81 ± 3.00% vs. -2.50 ± 2.7%, p = 0.009), the tendency for decrease in fat mass (-8.28 ± 8.86% vs. — 3.20 ± 5.09%, p = 0.068) and waist circumference (-5.91 ± 4.29% vs. -3.03 ± 4.01 %, p = 0.091) compared with G allele carriers. The association of rs7903146 TCF7L2 and rs1042714 ADRB2 with changes in total body weight was not observed (p&gt; 0.05).CONCLUSION: Single nucleotide polymorphisms rs7903146 TCF7L2 and rs1042714 ADRB2 influence on body fat composition in patients with early carbohydrate metabolism disorders in various types of treatment.

Association of FTO gene variant rs9939609 with hyperandrogenemia and fasting glucose\xa0levels in South Indian women with polycystic ovarian syndrome

BackgroundPolycystic ovary syndrome (PCOS) is a common endocrine–metabolic disorder due to genetic and environmental factors. Genetic variants located in intron 1 of Fat mass and obesity-associated (FTO) gene are associated with increased risk of obesity and metabolic disorders. This study aims to investigate the association of common FTO polymorphism rs9939609 in South Indian women with PCOS to assess its association with metabolic and endocrine parameters. FTO genotyping was done on 100 PCOS patients and 70 controls by Sanger sequencing.ResultsThe distribution of rs9939609 was observed between groups (28% TT, 57% TA, and 15% AA for PCOS and 37.1% TT, 51.4% TA, and 11.4% AA for the controls). In the PCOS group, across the carriers of different genotypes, a significant association was found between body mass index (BMI), fasting glucose levels, and testosterone with the presence of at least one risk allele of FTO rs9939609. Logistic regression analysis showed the association of fasting glucose levels and testosterone (OR 1.30 [1.03–1.63] and OR 5.83 [1.61–21.11], respectively) with FTO rs9939609.ConclusionsOur findings indicated that FTO SNP rs9939609 was not associated with PCOS, but suggested a significant association of rs9939609 with hyperandrogenemia, fasting glucose levels, and BMI in South Indian women with PCOS.

A systematic review and meta-analysis on the association between CD36 rs1761667 polymorphism and cardiometabolic risk factors in adults

The cluster of differentiation 36 (CD36) is one of the main receptors implicated in the pathogenesis of the cardiovascular disease. This study aimed to assess the association between CD36 rs1761667 polymorphism and cardiometabolic risk factors including body mass index (BMI), waist circumference (WC), total cholesterol (TC), triglyceride, HDL-C, LDL-C, blood pressure and fasting blood glucose (FBG). PubMed, EMBASE, Scopus, web of science, and Google Scholar were searched up to December 2021. Subgroup and meta-regression analyses were conducted to explore sources of heterogeneity. Eighteen eligible studies (6317 participants) were included in the study. In the overall analysis, a significant association was found between rs1761667 polymorphism of CD36 and TG in allelic (p < 0.001), recessive (p = 0.001) and homozygous (p = 0.006) models. A relationship between this polymorphism and HDL-C and FBG level was observed in the recessive genetic model. In the subgroup analysis, the A allele was associated with impaired lipid profiles (TC, LDL-C and HDL-C) in the Asian population. The influences of health status, design of the study, confounders, and other sources of heterogeneity should be considered when interpreting present findings. Cohort studies with large sample size and in different ethnicities are needed to confirm the relationship between rs1761667 SNP and cardiometabolic risk factors.

Association between glucokinase regulator gene polymorphisms and serum uric acid levels in Taiwanese adolescents

The glucokinase regulator gene (GCKR) is located on chromosome 2p23. It plays a crucial role in maintaining plasma glucose homeostasis and metabolic traits. Recently, genome-wide association studies have revealed a positive association between hyperuricemia and GCKR variants in adults. This study investigated this genetic association in Taiwanese adolescents. Data were collected from our previous cross-sectional study (Taipei Children Heart Study). The frequencies of various genotypes (CC, CT, and TT) or alleles (C and T) of the GCKR intronic single-nucleotide polymorphism (SNP) rs780094 and the coding SNP rs1260326 (Pro446Leu, a common 1403C-T transition) were compared between a total of 968 Taiwanese adolescents (473 boys, 495 girls) with hyperuricemia or normal uric acid levels on the basis of gender differences. Logistic and linear regression analyses explored the role of GCKR in abnormal uric acid (UA) levels. Boys had higher UA levels than girls (6.68 ± 1.29 and 5.23 ± 0.95 mg/dl, respectively, p < 0.001). The analysis of both SNPs in girls revealed that the T allele was more likely to appear in patients with hyperuricemia than the C allele. After adjusting for confounders, the odds ratio (OR) for hyperuricemia incidence in the TT genotype was 1.75 (95% confidence interval [CI] 1.02–3.00), which was higher than that in the C allele carriers in rs1260326 in the girl population. Similarly, the TT genotypes had a higher risk of hyperuricemia, with an OR of 2.29 (95% CI 1.11–4.73) for rs1260326 and 2.28 (95% CI 1.09–4.75) for rs780094, than the CC genotype in girl adolescents. The T (Leu446) allele of GCKR rs1260326 polymorphism is associated with higher UA levels in Taiwanese adolescent girls.

IDF21-0458 Associations of GCKR polymorphism with albuminuria and end-stage kidney disease in Chinese patients with type 2 diabetes

Background: Diabetes is the leading cause of end-stage kidney disease (ESKD) worldwide and is prevalent amongst Asians. The glucokinase regulator (GCKR) modulates glucokinase activity by forming an inhibitory complex and influences multiple metabolic pathways. Some studies have reported associations of GCKR polymorphisms with renal function and chronic kidney disease, however, the association of rs1260326 polymorphism with albuminuria and risk of ESKD remains unclear.

Interaction of night shift work with polymorphism in melatonin receptor 1B gene on incident stroke.

ObjectivesThe aim of this study was to investigate whether melatonin receptor type 1B (MTNR1B) rs10830963 polymorphism interacts with night shift work on the risk of incident stroke.MethodsThis study included individuals free of stroke at baseline from the UK Biobank. Night-shift work was assessed by the self-reported questions. MTNR1B rs10830963 was directly genotyped (CC, GC, and GG). Incident stroke was ascertained through hospital records and death registries. Cox proportional hazards models were employed to examine the associations of night shift work and MTNR1B rs10830963 with the risk of incident stroke.ResultsA total of 242 194 participants were finally included (mean age: 52.95 years; 51.63% women). Over 12-year follow-up, 3287 incident stroke events occurred. Night shift work increased the risk of incident stroke [hazard ratio (HR) 1.13, 95% confidence interval (CI) 1.00–1.28] after adjusting for socio-demographics, and this association attenuated after additional adjustment for lifestyle factors (HR 1.06, 95% CI 0.94–1.20). MTNR1B rs10830963 polymorphism modified the association between night shift work and incident stroke (Pfor interaction =0.010). In the Cox models adjusted for socio-demographics and lifestyle factors, among night-shift workers, minor allele G was associated with a reduced risk of incident stroke (GC versus CC, HR 0.74, 95% CI 0.58–0.95; GG versus CC, HR 0.65, 95% CI 0.40–1.06; Pfor trend=0.010); while night shift work was associated with a higher stroke risk only among MTNR1B rs10830963 CC carriers (HR 1.23, 95% CI 1.05–1.44) but not GC/GG carriers.ConclusionsThese results suggest that MTNR1B rs10830963 may potentially modify the associations between night shift work and incident stroke.

Correlation of Adiponectin Gene Polymorphisms rs266729 and rs3774261 With Risk of Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.

BackgroundIncreasing evidence has suggested an association of adiponectin gene polymorphisms rs1501299, rs2241766, rs266729 and rs3774261 with risk of nonalcoholic fatty liver disease (NAFLD). This correlation has been extensively meta-analyzed for the first two polymorphisms, but not the second two.MethodsThe PubMed, EMBASE, Google Scholar, and China National Knowledge Infrastructure databases were searched for relevant literature. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.ResultsA total of 10 case-control studies on rs266729 (2,619 cases and 1,962 controls) and 3 case-control studies on rs3774261 (562 cases and 793 controls) were included. Meta-analysis showed that rs266729 was associated with significantly higher NAFLD risk based on the following five models: allelic, OR 1.72, 95% CI 1.34-2.21, P < 0.001; recessive, OR 2.35, 95% CI 1.86-2.95, P < 0.001; dominant, OR 1.84, 95% CI 1.34-2.53, P < 0.001; homozygous, OR 2.69, 95% CI 1.84-3.92, P < 0.001; and heterozygous, OR 1.72, 95% CI 1.28-2.32, P < 0.001. This association between rs266729 and NAFLD risk remained significant for all five models among studies with Asian, Chinese and Caucasian samples. The rs2241766 polymorphism was associated with significantly higher NAFLD risk according to the recessive model (OR 1.87, 95% CI 1.15-3.04, P = 0.01).ConclusionPolymorphisms rs266729 and rs3774261 in the adiponectin gene may be risk factors for NAFLD. These findings may pave the way for novel therapeutic strategies, but they should be verified in large, well-designed studies.

Metabolic Syndrome but Not Fatty Liver-Associated Genetic Variants Correlates with Glomerular Renal Function Decline in Patients with Non-Alcoholic Fatty Liver Disease.

The association between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) has been extensively demonstrated. Recent studies have focused attention on the role of patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism in the association between NAFLD and CKD in non-metabolic adults and children, but the genetic impact on NAFLD-CKD association is still a matter of debate. The aim of the study was to investigate the impact of PNPLA3, transmembrane 6 superfamily member 2 (TM6SF2), membrane-bound O-acyltransferase domain containing 7 (MBOAT7) and glucokinase regulatory protein (GCKR) gene variants rather than metabolic syndrome features on renal function in a large population of NAFLD patients. The present study is a post hoc analysis of the Plinio Study (ClinicalTrials.gov: NCT04036357). PNPLA3, TM6SF2, MBOAT7 and GCKR genes were analyzed by using real-time PCR with TaqMan probes. Glomerular filtration rate (GFR) was estimated with CKD-EPI. We analyzed 538 NAFLD; 47.2% had GFR < 90 mL/min/1.73 m2 while 5.9% had GFR < 60 mL/min/1.73 m2. The distribution of genotypes was superimposable according to GFR cut-offs. Results from the multivariable regression model did not show any correlation between genotypes and renal function. Conversely, metabolic syndrome was highly associated with GFR < 90 mL/min/1.73 m2 (odds ratio (OR): 1.58 [1.10–2.28]) and arterial hypertension with GFR < 60 mL/min/1.73 m2 (OR: 1.50 [1.05–2.14]). In conclusion, the association between NAFLD and CKD might be related to the shared metabolic risk factors rather than the genetic NAFLD background.

Possible Role of rs7903146 Polymorphism of the Transcription Factor 7-Like 2 Gene in Genetic Predisposition to Type 2 Diabetes.

&lt;b&gt;Background and Objective:&lt;/b&gt; The association of rs7903146 polymorphism of TCF7L2 gene with Type 2 diabetes mellitus found almost in all ethnic groups. Therefore, the current study focused on estimating this association in the Azerbaijan population for the 1st time. &lt;b&gt;Materials and Methods:&lt;/b&gt; A study was conducted on 110 patients with Type 2 diabetes mellitus and 115 healthy controls. The biochemical parameters were analyzed and calculated with an independent t-test and Fisher exact test. DNA extracted from the blood samples run in PCR. PCR was used to detect the presence of TCF7L2 rs7903146 C/T polymorphism and the products of the PCR were visualized in a 1.5% gel electrophoresis. &lt;b&gt;Results:&lt;/b&gt; According to the obtained data, T allele and TT genotype of rs7903146 polymorphism strongly correlated with the risk for Type 2 diabetes (odds ratio of 1.68 for T allele and p = 0.007, odds ratio of 3.9 for TT genotype, p = 0.0028). These results were adjusted by applying the recessive model (p = 0.003). Moreover, the biochemical parameters also show a significant difference in the fasting glucose level (p = 0.0001), fasting insulin (p = 0.0001), BMI (p = 0.0002) and age (p = 0.015) inpatient and control groups. &lt;b&gt;Conclusion:&lt;/b&gt; Based on the results, the TCF7L2 rs7903146 (C>T) polymorphism is the genetic risk factor related to Type 2 diabetes in the Azerbaijan population.

Association of gene polymorphisms with body weight changes in prediabetic patients

BackgroundRecent research has demonstrated that Type 2 Diabetes (T2D) risk is influenced by a number of common polymorphisms, including MC4R rs17782313, PPARG rs1801282, and TCF7L2 rs7903146. Knowledge of the association between these single nucleotide polymorphisms (SNPs) and body weight changes in different forms of prediabetes treatment is still limited. The aim of this study was to investigate the association of polymorphisms within the MC4R, PPARG, and TCF7L2 genes on the risk of carbohydrate metabolism disorders and body composition changes in overweight or obese patients with early carbohydrate metabolism disorders.Methods and resultsFrom 327 patients, a subgroup of 81 prediabetic female patients (48.7 ± 14.8 years) of Eastern European descent participated in a 3-month study comprised of diet therapy or diet therapy accompanied with metformin treatment. Bioelectrical impedance analysis and genotyping of MC4R rs17782313, PPARG rs1801282, and TCF7L2 rs7903146 polymorphisms were performed. The MC4R CC and TCF7L2 TT genotypes were associated with increased risk of T2D (OR = 1.46, p = 0.05 and OR = 2.47, p = 0.006, respectively). PPARG CC homozygotes experienced increased weight loss; however, no additional improvements were experienced with the addition of metformin. MC4R TT homozygotes who took metformin alongside dietary intervention experienced increased weight loss and reductions in fat mass (p < 0.05).ConclusionsWe have shown that the obesity-protective alleles (MC4R T and PPARG C) were positively associated with weight loss efficiency. Furthermore, we confirmed the previous association of the MC4R C and TCF7L2 T alleles with T2D risk.

Association of Polymorphisms in Estrogen Receptor Genes (ESR1 and ESR2) with Osteoporosis and Fracture-Involvement of Comorbidities and Epistasis.

Single-nucleotide polymorphisms (SNPs) in the ESR1/ESR2 genes play a role in osteoporosis (OP). Our objective was to determine associations of polymorphisms in ESR genes with OP and fracture, SNP-SNP interactions, and involvement of comorbidities. We analyzed 170 Mexican osteoporotic women (FNOP), 173 with hip fracture (HFx), and 210 controls. The SNPs, ESR1 rs2234693CC, rs851982CC and rs1999805AA, were associated with reduced OP risk (odds ratios [ORs] = 0.35, 0.40 and 0.32, respectively; p < 0.05); rs2234693CC was associated with reduced fracture risk (OR = 0.24; p < 0.05). The obese/overweight carriers of rs9340799GG had a lower OP (OR = 0.15, p = 0.016) and fracture (OR = 0.12, p = 0.0057) risk. The rs9479055AA and rs3020404AA hypertensive carriers had a higher OP risk (OR = 5.96, p = 0.032; and OR = 5.29, p = 0.02, respectively). In addition, rs3020404AA had a higher risk of fracture (OR = 4.90, p = 0.045). The rs2228480GG hypertensive carriers had a higher risk of fracture (OR = 6.22, p = 0.0038). We found a synergic relation between the ESR1 rs3020331 and rs1999805 in femoral neck OP and HFx. The rs2234693 (PvuII) and rs9340799 (XbaI) polymorphisms are associated with a high risk forming a haplotype. The epistasis analysis suggests the contribution of both genes (ESR1/ESR2) to the risk of OP and fracture. Epistasis and involvement of obesity and hypertension lead to a significant modification of the risk.

What is the role of cardiorespiratory fitness and sedentary behavior in relationship between the genetic predisposition to obesity and cardiometabolic risk score?

BackgroundGenetic factors along with inadequate lifestyle habits are associated with the development of cardiometabolic alterations. Thus, the present study aimed to examine the role of sedentary behavior on the relationship between rs9939609 polymorphism (fat mass and obesity-associated gene-FTO) and cardiometabolic risk score according to cardiorespiratory fitness (CRF) levels in children and adolescents.MethodsA cross-sectional study with 1215 children and adolescents (692 girls), aged between 6 and 17 years. Screen time as a marker of sedentary behavior was evaluated through a self-reported questionnaire and CRF was estimated using the 6-min walking and running test. The genotyping of the FTO rs9939609 polymorphism was performed using a real-time polymerase chain reaction. Clustered cardiometabolic risk score (cMetS) was calculated by summing z-scores of total cholesterol/high-density lipoprotein cholesterol ratio, triglycerides, glucose, systolic blood pressure, and waist circumference, and dividing it by five. Moderation analyses were tested using multiple linear regression models.ResultsThe coefficient of the interaction term of FTO (rs9939609) and screen time indicated that screen time was a significant moderator on the relationship between FTO rs9939609 polymorphism and cMetS (p = 0.047) in children and adolescents classified with low CRF (β = 0.001; 95% CI = 0.001; 0.002). It was observed a significant association between genotype risk (AA) of FTO polymorphism and cMetS, in participants that spent more than 378 min a day in front of screen-based devices (β = 0.203; 95% CI = 0.000; 0.405). No interaction term was found for those with high CRF.ConclusionsHigh sedentary behavior seems to influence the relationship between genetic predisposition to obesity and cardiometabolic risk factors in children and adolescents with low CRF.

Association of glucokinase gene and glucokinase regulatory protein gene polymorphisms with gestational diabetes mellitus: A case–control study

ObjectivesThe aim of this study was to investigate the association of glucokinase (GCK) gene, glucokinase regulatory protein (GCKR) gene polymorphisms with the susceptibility to GDM in Chinese population.Research design and methods.This case-control study included 835 GDM patients and 870 non-diabetic pregnant women who had their prenatal examinations at 24–28 gestational weeks at the Maternal and Child Health Hospital of Hubei Province from January 15, 2018 to March 31, 2019. The nurses were trained to collect clinical information and blood samples. The candidate single nucleotide polymorphism (SNPs, GCK rs1799884, rs4607517, rs10278336, rs2268574, rs730497 and GCKR rs780094, rs1260326) were genotyped on Sequenom Massarray platform. Statistical analysis including independent sample t test, chi-square test, logistic regression and one-way ANOVA were performed to evaluate the differences in allele and genotype distributions and their correlations with the odds of GDM. ResultsThere were statistically significant differences in age, pre-gestational BMI, education level and family history of diabetes between case and control group (P < 0.05). After adjusting for these confounders, GCK rs1799884 was still significantly associated with GDM (P < 0.05), but there were no significant associations between rs4607517, rs10278336 and rs2268574, rs780094 and rs1260326 polymorphisms and GDM odds (P > 0.05). In addition, the pregnant women with rs4607517 TT genotype had the significantly higher fasting blood glucose level than CC genotype (P < 0.05). ConclusionGCK rs1799884 mutation is associated with higher GDM odds in Chinese population. Further larger studies are needed to explore the association between GCK and GCKR polymorphisms and GDM susceptibility.

Association between Genetic Polymorphisms and Risk of Kidney Posttransplant Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Objectives The purpose of this study was to clarify the role of genetic factors on posttransplant diabetes mellitus (PTDM) risk. Methods Relevant publications were systematically retrieved from PubMed, EMBASE, and the Cochrane Library up to December 2020. Data from eligible case-control and cohort studies were extracted for qualitative and quantitative analyses. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the association between gene polymorphisms and PTDM in the quantitative meta-analysis. Results A total of 43 eligible articles were identified, and 16 studies on 9 DNA variants from 8 genes were included in the meta-analysis. TCF7L2 rs7903146 was significantly associated with PTDM risk in 5 genetic models (OR (95% CI): allelic: 1.59 (1.17–2.16), P=0.003; dominant recessive: 1.62 (1.14, 2.31), P=0.007; recessive: 1.87 (1.18, 2.94), P=0.007; homozygote: 2.21 (1.23, 3.94), P=0.008; and heterozygote 1.50 (1.08, 2.10), P=0.017). KCNQ1 rs2237892 was significantly correlated with PTDM risk in 3 genetic models (allelic: 0.68 (0.58, 0.81), P < 0.001; dominant: 0.6 (049, 0.74), P < 0.001; and heterozygote: 0.61 (0.48, 0.76), P < 0.001). KCNJ11 rs5219 was significantly linked with PTDM in the recessive genetic model (1.59 (1.01, 2.50), P=0.047). No significant correlations of PTDM with TCF7L2 rs12255372, SLC30A8 rs13266634, PPARγ rs1801282, CDKN2A/B rs10811661, HHEX rs1111875, and IGF2BP2 rs4402960 polymorphisms were found. Conclusions The gene polymorphisms of TCF7L2 rs7903146, KCNQ1 rs2237892, and KCNJ11 rs5219 may predispose kidney transplant recipients to PTDM. Large sample size studies on diverse ethnic populations were warranted to confirm our findings.