Rs9939609 Polymorphism Research Articles

The Effect of Association between Fat Mass and Obesity-associated Gene Polymorphism (rs9939609) on the Body Composition of Older People: A Systematic Review.

The aging population is growing faster than any other age group worldwide. Associated with aging, the prevalence of overweight and obesity is a potential risk factor for the development and aggravation of numerous pathologies. A genetic factor often associated with obesity is the fat mass and obesity-associated (FTO) (rs9939609) gene polymorphism, which has been extensively investigated in children, young, and adults. However, few studies have been carried out on the older population. This review aimed to verify the influence of the FTO (rs9939609) gene polymorphism on the body composition of the older population. We conducted a systematic review and meta-analysis on PubMed, Scielo, and LILACS databases. Statistical analysis for meta-analysis was performed using mean values of Body Mass Index (BMI) and standard deviations. The results did not show significant differences between FTO genotypes and BMI values (-0.32, 95% CI -0.45 to -0.19, I2 = 0%, p = 0.52). However, 59% of the studies identified some influence on body composition, obesity, or comorbidities. Few publications verify FTO polymorphism effects on specific groups of the older population, suggesting a reduction in the influence of this gene on the BMI with advancing age. However, we believe that more controlled studies in older populations should be performed.

Clinical signs of type 1 diabetes are associated with type 2 diabetes marker transcription factor 7-like 2 polymorphism.

We aimed to assess the distribution of transcription factor 7-like 2 gene TCF7L2 (rs7903146) polymorphism and to find possible associations between TCF7L2 and the characteristics of type 1 diabetes. We studied 190 newly diagnosed type 1 diabetes patients (median age 12.7 years, range 2.0-72.5) and 246 controls (median age 23.8 years, range 1.4-81.5) for TCF7L2 single nucleotide polymorphism. We determined anti-islet autoantibodies, random C-peptide levels, diabetes associated HLA DR/DQ haplotypes and genotypes in all patients. There were no differences in the distribution of TCF7L2 single nucleotide polymorphism between patients and controls. However, patients with in type 1 diabetes, after adjusting for age and sex, subjects carrying C allele were at risk for a C-peptide level lower than 0.5 nmol/L (OR 5.65 [95% CI: 1.14-27.92]) and for zinc transporter 8 autoantibody positivity (5.22 [1.34-20.24]). Participants without T allele were associated with a higher level of islet antigen-2 autoantibodies (3.51 [1.49-8.27]) and zinc transporter 8 autoantibodies (2.39 [1.14-4.99]). The connection of TCF7L2 polymorphism with zinc transporter 8 and islet antigen-2 autoantibodies and C-peptide levels in patients supports the viewpoint that TCF7L2 is associated with the clinical signs and autoimmune characteristics of type 1 diabetes. The mechanisms of the interaction between the TCF7L2 risk genotype and anti-islet autoantibodies need to be studied further.

NAFLD in Polycystic Ovary Syndrome: Association with PNPLA3 and Metabolic Features.

The aim of this study was to determine the frequency of the rs738409 polymorphism in the patatin-like phospholipase domain containing 3 (PNPLA3) gene in patients with polycystic ovary syndrome (PCOS) and its impact on nonalcoholic fatty liver disease (NAFLD) risk and severity. We also evaluated other risk factors associated with NAFLD and advanced fibrosis. This was a cross-sectional study involving 163 patients with PCOS at a tertiary center. Genotyping for the PNPLA3 polymorphism was undertaken using a TaqMan assay. The degree of fibrosis was defined by transient elastography. The prevalence of NAFLD was 72.4%, and the polymorphism was heterozygous in 41.7% and homozygous in 8% of patients. Homeostasis model assessment of insulin resistance ≥ 2.5 was the main factor associated with the risk of developing NAFLD (OR = 4.313, p = 0.022), and its effect was amplified by the polymorphism (OR = 12.198, p = 0.017). Age > 32 years also conferred a higher risk for NAFLD. HDL values ≥ 50 mg/dL conferred protection against the outcome. Metabolic syndrome (OR = 13.030, p = 0.020) and AST > 32 U/L (OR = 9.039, p = 0.009) were independent risk factors for advanced fibrosis. In women with PCOS, metabolic characteristics are more relevant than PNPLA3 polymorphism regarding the risk for NAFLD and its advanced forms, but these factors can act synergistically, increasing disease risk.

ЭФФЕКТИВНОСТЬ ЛЕЧЕНИЯ ЖЕНЩИН С ПОСТМЕНОПАУЗАЛЬНЫМ ОСТЕОПОРОЗОМ В ЗАВИСИМОСТИ ОТ ПОЛИМОРФИЗМА RS2234693 ГЕНА ЭСТРОГЕНОВОГО РЕЦЕПТОРА 1 ТИПА

Pharmacogenetic testing, that is promising technology for personalized medicine, is already being introduced into clinical practice. Pharmacogenetic approach is especially necessary when prescribing treatment for patients with osteoporosis, because anti-osteoporotic drugs effect can be assessed only after 12 months or more after therapy start. On this basis, aim of study was to estimate alendronic acid effectiveness in women with postmenopausal osteoporosis depending on rs2234693 polymorphism of estrogen receptor type 1 gene (ESR1). Material and methods. 136 patients were included to research. The studies in women were performed twice - before and 12 months after osteoporosis treatment, that included alendronic acid standard doses. Evaluation of 12-month therapy effectiveness was carried out according to bone mineral density increase based on X-ray osteodensitometry. Genotype of rs2234693 polymorphism of ESR1 gene was determined by real-time PCR. Results. Women with postmenopausal osteoporosis after alendronic acid 12-month course demonstrated significant (p<0.001) mineral density increase in various parts of skeleton - lumbar vertebrae L1-L4 (4.26% [1.00; 6.95]), left proximal region and femoral neck (2.76% [0.00; 5.95] and 2.42% [-1.41; 5.53], respectively) and right ones (3.76%[-0.20; 6.65] and 3.27% [0.00; 7.18], respectively). Patients with TT genotype of ESR1 gene rs2234693 polymorphism had lower (p<0.05) increase in mineral density of lumbar vertebrae L1-L4 (2.53% [-0.28; 5.54]) compared to all other patients (4.71% [1.75; 8.08]) or to women with CC genotype (5.52% [1.66; 9.12]). Conclusion. rs2234693 polymorphism of ESR1 gene testing in patients with postmenopausal osteoporosis before antiosteoporotic drugs prescription should be used for individualization of treatment regimens and therapy effectiveness enhancement.

Interaction between MTNR1B polymorphisms and lifestyle intervention on pregnancy outcomes

Abstract Background Interactions between polymorphisms of the melatonin receptor 1B gene (MTNR1B) and lifestyle intervention for gestational diabetes have been described. Whether these are specific for physical activity or healthy eating intervention is unknown. Objectives To assess the interaction between MTNR1B rs10830962 and rs10830963 polymorphisms and lifestyle interventions during pregnancy. Methods Women with a BMI of ≥ 29 kg/m2 (n = 436) received counseling on healthy eating (HE), physical activity (PA) or both. The control group received usual care. The analysis had a factorial design with comparison of HE versus no HE and PA versus no PA. Maternal outcomes at 24-28 weeks were gestational weight gain (GWG), maternal fasting glucose, insulin, insulin resistance (HOMA-IR), and development of GDM. Interaction between receiving either HE or PA intervention and genotypes of both rs10830962 and rs10830963 was assessed using multilevel regression analysis. Results GDM risk was increased in women homozygous for the G allele of rs10830962 or rs10830963 (OR 2.60 [95% CI 1.34, 5.06] and 2.83 [1.24, 6.47], respectively). Significant interactions between rs10830962 and interventions were found: In women homozygous for the G allele, but not in the other genotypes, the PA intervention reduced maternal fasting insulin (beta -0.16 [95%CI -0.33, 0.02], p = 0.08) and HOMA-IR (-0.17 [-0.35, 0.01], p = 0.06). In heterozygous women, HE intervention had no effect, whereas in women homozygous for the C allele, HE intervention reduced GWG (-1.6 kg [-2.4, -0.8]). Discussion In women homozygous for the risk allele of MTNR1B rs10830962, GDM risk was increased and PA intervention might be more beneficial than HE intervention for reducing maternal insulin resistance. Key messages

MiR-516a-3P, a potential circulating biomarker in hepatocellular carcinoma, correlated with rs738409 polymorphism in PNPLA3.

Aim: The aim was to investigate the expression profile of miR-516a-3P and its correlation with thePNPLA3 rs738409 polymorphism in Egyptian hepatitis C virus (HCV) and hepatocellular carcinoma (HCC) patients. Materials & methods: miR-516a-3P was quantified and rs738409 was genotyped by quantitative reverse transcription PCR. Results: miR-516a-3P was significantly upregulated in HCC patients compared with HCV patients (p=0.001). Receiver operating characteristic curve analysis confirmed that miR-516a-3P discriminates HCC from HCV (p=0.001). A significant (p=0.015) correlation between miR-516a-3p level and PNPLA3 rs738409 genotypes was recorded in HCV patients, yet it was not recorded in either healthy individualsor HCC patients. miR-516a-3p level was significantly (p=0.001) higher in HCV patients carrying the rs738409 GG genotype than in those carrying the CC genotype. Conclusion: miR-516a-3P is a potential biomarker in HCC. PNPLA3 rs738409 GG carriers affect miR-516a-3P expression in HCV, and this may highlight a new mechanism in liver disease.

The effect of FTO rs9939609 polymorphism on the association between colorectal cancer and dietary fiber.

BackgroundGene polymorphisms may explain the controversy on the association between colorectal cancer (CRC) and dietary fibers. The purpose of this study was to investigate the effect of fat mass and obesity-associated (FTO) rs9939609 polymorphism on the association between colorectal cancer and dietary fiber.MethodsThis case-control study was conducted on 160 CRC cases and 320 healthy controls in Tehran, Iran. The participants' food intake was assessed using a semi-quantitative food frequency questionnaire (FFQ). The frequency of rs9939609 FTO polymorphism in the case and control groups was determined using the tetra-primer amplification refractory mutation (tetra-ARMS) method.ResultsIn the participants with the TT genotype of the FTO rs9939609, the cases had higher BMI and lower intake of dietary fiber compared to the controls (P = 0.01). Among A allele carriers of FTO rs9939609 polymorphism, the cases had higher BMI (P = 0.04) and lower intake of total fiber (P = 0.02) and soluble fiber (P = 0.02). An inverse association was found between CRC and dietary fiber intake among those with the AA/AT FTO rs9939609 genotype after adjusting for age, sex, smoking, alcohol consumption, physical activity, BMI, and calorie intake (OR = 0.9, CI 95%:0.84–0.92, P < 0.05).ConclusionThis study found a link between higher dietary fiber consumption and a lower risk of CRC in A-allele carriers of FTO rs9939609 polymorphism. Future studies are needed to identify the underlying mechanisms of the association between CRC and dietary fibers in people with different FTO genotypes.

TCF7L2 gene associated postprandial triglyceride dysmetabolism- a novel mechanism for diabetes risk among Asian Indians.

Aim TCF7L2 gene is believed to increase the risk of T2DM by its effects on insulin secretion. However, the exact mechanism of this enhanced risk is not clearly known. While TCF7L2 gene has been shown to affect lipid metabolism, these effects have remained largely unexplored in the context of diabetes risk.MethodsPostprandial lipid responses to a standardized fat challenge test were performed in 620 Asian Indian subjects (310 with NGT and 310 with T2DM/prediabetes) and compared between the risk and wild genotypes of the rs7903146 TCF7L2 gene. In 30 subjects scheduled to undergo abdominal surgery (10 each with NGT, Prediabetes and T2DM), adipocyte TCF7L2 gene expression was also performed by real time qPCR and confirmed by protein expression in western blot.ResultsT allele of rs7903146 TCF7L2 gene was confirmed as the risk allele for T2DM (OR=1.8(1.2-2.74), p=0.005). TT+CT genotypes of rs7903146 TCF7L2 gene showed significantly higher 4hrTg (p<0.01), TgAUC (p<0.01), peakTg (p<0.01) as well as higher postprandial plasma glucose (p=.006) levels and HOMA-IR (p=0.03) and significantly lower adiponectin levels (p=0.02) as compared to CC genotype. The expression of TCF7L2 gene in VAT was 11-fold higher in prediabetes group as compared to NGT (P<0.01) and 5.7-fold higher in T2DM group as compared to NGT group(P=0.003) and was significantly associated with PPTg and glucose levels.ConclusionThere is significant PPTg dysmetabolism associated with the risk allele of rs7903146 polymorphism as well as adipocyte expression of TCF7L2 gene. Significant upregulation of TCF7L2 gene expression in VAT that correlates with PPTg and glycaemia is also seen in Asian Indians with glucose intolerance. Modulation of PPTg metabolism by TCF7L2 gene and the resultant PPHTg may be a novel mechanism that contributes to its diabetes risk in them.

Associations of PNPLA3 rs738409 Polymorphism with Plasma Lipid Levels: A Systematic Review and Meta-Analysis.

Accumulating evidence has shown that the rs738409 polymorphism of patatin-like phospholipase domain-containing 3 (PNPLA3) is associated with non-alcoholic fatty liver disease (NAFLD). Since NAFLD has been reported to be associated with lipid metabolism, this study is conducted to explore whether the rs738409 polymorphism of PNPLA3 was associated with lipid levels. By searching PubMed and the Cochrane database from May 31, 2020, to June 30, 2021. Sixty-three studies (81 003 subjects) were included for the analysis. The consistent findings for the associations of rs738409 polymorphism with lipid levels were the significantly decreased triglycerides (TG) (SMD=-0.04, 95% CI=-0.07 to -0.01, p=0.02) and total cholesterol (TC) (SMD=-0.03, 95% CI=-0.05 to -0.01, p<0.01) levels. Subgroup analysis indicated that the associations of rs738409 polymorphism with TG and TC levels were stronger in Caucasians, obesity patients, and adult subjects than in Asians, T2DM patients, and children subjects. The rs738409 polymorphism of PNPLA3 was associated with lower TG and TC levels in Caucasians, obese and adult subjects, which may contribute to the reduced coronary artery disease (CAD) risk between PNPLA3 rs738409 polymorphism and CAD.

The influence of the rs2010963 polymorphism of the VEGFA gene on the response to the treatment of the “wet” form of age-related macular degeneration

Annotation. Age-related macular degeneration is one of the main causes of vision loss in the elderly. By 2040, the population with age-related macular degeneration (AMD) is expected to reach about 288 million. It was hypothesized that anti-VEGF therapy would significantly improve the vision and quality of life of patients with “wet” AMD. However, approximately one-third of patients do not benefit from this therapy, including due to macular fibrosis or retinal atrophy. It is believed that the role of genetic predisposition may also influence treatment resistance. Therefore, the aim of the study was to identify the response to treatment with aflibercept in patients with “wet” AMD with polymorphism variants rs2010963 of the VEGFA gene. The research group included 162 people who had a confirmed “wet” form of AMD, in contrast to which 105 people were included in the comparison group. The “wet” form of AMD was detected with the help of optical coherence tomography using the ILM-RPE parameter, while the patients received monthly intravitreal injections of the AVGF drug aflibercept (50 μl of solution – the recommended dose). Real-time polymerase chain reaction was used to determine the rs2010963 polymorphism of the VEGFA gene. Statistical processing of the obtained results was carried out using Statistica 10.0 and SPSS 23.0 programs. It was established that the presence of the mutant C allele increases the risk of resistance to anti-VEGF therapy both after the first injection and after the full course of treatment (p&lt;0.05). A strong influence of the polymorphism after the therapy was observed in the areas of OCT 2, which corresponds to the inner upper part of the retina (OR=5.89; 95% CI 3.31 – 10.49) and OCT 3, which corresponds to the central area of ​​the retina (OR=4, 76; 95% CI 2.79 – 8.13). At the same time, there is an influence of mutant genotypes on treatment: yes, carrying both the heterozygous variant of ONP and the homozygous variant for the minor allele significantly contributed to the emergence of resistance to treatment (p&lt;0.05). A pronounced degree of association of rs2010963 of the VEGFA gene with the emergence of resistance to the action of anti-VEGF drugs was revealed. Thus, the heterogeneity of RR and 95% CI indicators in different areas of the retina likely indicates a “zone-dependent” effect of rs2010963 of the VEGFA gene on the retina, which may be related to the peculiarities of its functioning and pathogenetic effect on the organ of vision.

The impact of polymorphism in PNPLA3 and TM6SF2 genes on the susceptibility and survival of hepatitis C-related hepatocellular carcinoma

BackgroundGenetic variants of Patatin-like phospholipase domain-containing protein 3 (PNPLA3) and transmembrane 6 superfamily member 2 (TM6SF2) genes have been reported with the development of hepatocellular carcinoma (HCC). This study aims to explore the role of The PNPLA3 rs738409 and TM6SF2 rs58542926 single-nucleotide polymorphisms (SNPs) on the incidence and survival of HCV-induced HCC in Egyptians.Methods and resultsThis case-control study included (120) HCC and (144) hepatitis C virus (HCV) patients. Baseline clinical, laboratory, tumor characteristics data, HCC recurrence, and overall survival were collected. PNPLA3 rs738409 and TM6SF2 rs58542926 polymorphism were detected by TaqMan allelic discrimination assay. We found that HCC patients were significantly older with male predominance. A significant difference between the TT genotypes of TM6SF2 frequency was observed in HCC compared with HCV patients. Moreover, the T allele of TM6SF2 distributions revealed a significant contribution to the different stages of HCC (p=0.03). Both PNPLA3 rs738409 and TM6SF2 rs58542926 variants showed a significant relation with treatment response according to the modified RECIST criteria. Age and diabetes mellitus were the independent factors associated with the development of HCC by multivariate regression analysis.ConclusionsTM6SF2 rs58542926 polymorphism, not PNPLA3 rs738409, could be implicated in the development of HCV-induced HCC and its progression.

Evaluation of the involvement of PPARG2 gene rs1801282 polymorphism in the pathogenesis of bronchial asthma with obesity in children

Introduction. Features of the clinical course of bronchial asthma in children with obesity made it possible to identify a special phenotype, when the presence and severity of obesity determine a more severe course of asthma and a worse response to asthma therapy. Asthma, like obesity, is recognized as a classic example of multifactorial diseases, which are based on a rather complex gene network. Studying the genetic basis of both of these complex traits and linking them to the asthma phenotype should contribute to our understanding of the overall genetic basis of these pathological disorders.Aim. Evaluation of the clinical and genetic significance of the rs1801282 polymorphism of the PPARG2 gene (34C&gt;G, p.Pro12Ala) in children with asthma and obesity.Materials and methods. 161 children with asthma were examined, including 59 patients with obesity 1-3 degrees. The examination included general clinical, functional, instrumental methods. The level of asthma control was determined according to the GINA criteria (2018). The study of gene polymorphisms was carried out by the real-time polymerase chain reaction.Results. An analysis of the frequencies of the PPARG2 gene polymorphism in children with bronchial asthma did not reveal any differences from the control group healthy people. In 61% of children with asthma and obesity, there was no control over the disease, which was associated with the G allele (OR 2.4 [95% CI: 1.09‒5.30], p=0.0281). An increase in the activity of lactate dehydrogenase and a decrease in the membrane potential of mitochondria in peripheral blood lymphocytes in children with the GG genotype were revealed, which may indirectly affect the level of disease control.Conclusion. The comorbidity of asthma and obesity in children affects the control of the disease. This manifests itself through immune mechanisms that play a key role in energy homeostasis and mitochondrial dysfunction of immunocompetent blood cells. The G-allele of the PPARG2 gene can be a marker of the lack of control over the disease in obese children with asthma. The pathogenetic significance of this polymorphism requires further study.

Association and interaction of the MC4R rs17782313 polymorphism with plasma ghrelin, GLP-1, cortisol, food intake and eating behaviors in overweight/obese Iranian adults

BackgroundRecent studies have shown that obesity is largely influenced by heredity and created by the interactions between several genes and environmental and behavioral factors. This study aimed to examine association between variant rs17782313 near melanocortin-4 receptor (MC4R) gene and behavioral and hormonal factors then evaluated interactions between variant MC4R rs17782313 with behavioral and hormonal factors on obesity.MethodsThis cross-sectional study included 403 subjects, overweight and/or obesity, aged 20–50 years from Iran. The MC4R rs17782313 data were measured by the PCR–RFLP method. Dietary intake, physical activity, stress, anxiety, depression, appetite and emotional eating were assessed by using validated questionnaires. Ghrelin, glucagon-like peptide-1 and cortisol were measured by radioimmunoassay in plasma samples. Participants were also divided into three groups based on rs17782313 genotype and BMI.ResultsAfter adjustment for age, gender, energy intake and PA, significant associations were observed between food intake, appetite, emotional eating, stress and physical activity with MC4R rs17782313 (p ˂0.05). Also, significant interactions were observed between fat intake (p-interaction = 0.002), protein intake (p-interaction = 0.01), energy intake (p-interaction = 0.01), emotional eating (p-interaction = 0.02), appetite (p-interaction = 0.04), stress (p-interaction = 0.04), ghrelin (p-interaction = 0.03), cortisol (p-interaction = 0.04) and physical activity (p-interaction = 0.04) and MC4R rs17782313 in terms of BMI.ConclusionInteractions between the CC genotype and high intakes of fat and energy, emotional eating, high appetite, and too much stress with high levels of cortisol and ghrelin probably can have an effect on BMI in overweight/obese subjects.

Body fat, cardiovascular risk factors and polymorphism in the FTO gene: randomized clinical trial and different physical exercise for adolescents

ObjectiveTo investigate the effects of different physical exercise programs and polymorphisms of the FTO (fat mass and obesity-associated gene) on body composition and cardiovascular risk factors in adolescents with overweight and obesity. MethodsA randomized, parallel, double-blind clinical trial consisting of the adolescent overweight from the state public network, in a simple representative random sample, who participated in an aerobic exercise or weight training intervention for 10 weeks. Anthropometry, body composition, biochemical markers, sexual maturation, and rs9939609 polymorphism in the FTO gene were assessed. 347 adolescents had their characterization of nutritional status. 72 individuals with overweight and obesity were invited to participate. 39 remained for the start of the program and were randomly allocated to both types of intervention. In the end, 26 subjects participated in the intervention programs, with 12 and 14 in the aerobic and weight training programs, respectively. ResultsHeterozygous and homozygous bearers of risk allele A participating in the aerobic program showed improvements in glycemia (p = 0.002) and total cholesterol (p = 0.023) and a reduction in body fat mass (p = 0.041). The weight training program reduced glycemia in patients with the risk allele A (p = 0.027). Cameron's stage four sexual maturation participants were 2.1 times more likely to improve their body fat (CI = 1.31-3.39). ConclusionAerobic exercises produced exclusively a significant decrease in fat mass and total cholesterol in patients with risk allele A. Distinct physical exercise programs may cause diverse changes in risk variables related to the health of adolescents.

Association of rs738409 Polymorphism in Adiponutrin Gene with Liver Steatosis and Atherosclerosis Risk Factors in Greek Children and Adolescents.

Non-alcoholic fatty liver disease (NAFLD) shares several risk factors with atherosclerosis, as it is associated with components of the metabolic syndrome. However, genetic variations have also been linked to the risk of NAFLD, such as adiponutrin/patatin-like phospholipase domain-containing the protein 3 (PNPLA3) rs738409 polymorphism. The aim of the study was to determine the associations of thePNPLA3 rs738409 polymorphism with NAFLD and atherosclerosis risk factors in children and adolescents from northern Greece. A total of 91 children/adolescents who followed a Mediterranean eating pattern with no particular restrictions were studied. They were divided into three subgroups, according to their body mass index (BMI) and the presence or absence of liver disease. Diagnosis of NAFLD was based on a liver ultrasound, while the distribution of the PNPLA3 rs738409 polymorphism was investigated in all the participants. From the components of metabolic syndrome, only BMI, waist circumference, blood pressure, and the homeostasis model of insulin resistance (HOMA-IR) differed significantly between groups. The rs738409 polymorphism was significantly associated with BMI and NAFLD, while lipid values had no significant association with either NAFLD or gene polymorphism. This study shows that in Greekchildren, there is a significant association between the rs738409polymorphism in the PNPLA3 gene and hepatic steatosis, regardless of bodyweight.

Associations between rs2241766 and rs3774261 polymorphisms in ADIPOQ gene and atopic dermatitis

Atopic dermatitis (AD) is a common skin condition that affects both children and adults. Adipokines have been shown to play a role in the pathogenesis of AD. In the current study, the association between adiponectin gene (ADIPOQ) polymorphisms and AD was investigated. In addition, changes in serum adiponectin levels in AD patients were examined. Restriction fragment length polymorphism-PCR technique was used to genotype ADIPOQ SNPs. The ELISA assay was used to measure serum Adiponectin levels. A total of 324 participants (162 AD and 162 healthy controls) were included in the study. The frequency of the GG genotype of rs3774261 was higher in the AD group (44.5%) than in the control group (32.7%, P<0.05). Regarding the rs2241766 SNP, the frequency of the GG genotype was higher in the AD group (10.5%) than in the control group (3.1%), while the frequency of the TT genotype was lower (P<0.001) in the AD group (35.8%) than the control group (57.4%). Moreover, the GG haplotype of rs3774261 and rs2241766 significantly increased the risk of AD by about 2-fold (P<0.05). Finally, serum adiponectin levels were lower in the AD group than in the control group (P<0.05). These results indicate an association of the rs2241766 and rs3774261 SNPs with the risk of developing AD among the population examined.

The relationship between fat mass and obesity associated gene polymorphism rs9939609 and resting cerebral blood flow in a midlife sample with overweight and obesity.

BackgroundThe single nucleotide polymorphism (SNP) rs9939609 in the fat mass and obesity associated fat mass and obesity associated gene (FTO) gene has been linked with increased BMI in adults. Higher BMI has been associated with poor brain health and may exert deleterious effects on neurocognitive health through cerebral hypoperfusion. However, it is unclear if there is a relationship between the FTO genotype and cerebral perfusion, or whether FTO genotype moderates the effects of weight loss on cerebral perfusion. Using data from a randomized controlled behavioral weight loss trial in adults with overweight and obesity, we tested (1) whether carriers of the A allele for FTO rs9939609 demonstrate different patterns of resting cerebral blood flow (rCBF) compared to T carriers, and (2) whether the FTO genotype moderates the effects of weight loss on rCBF. We hypothesized that carriers of the A allele would exhibit lower resting CBF in frontal brain areas compared to T/T homozygotes at baseline, and that intervention-induced weight loss may partially remediate these differences.Methods and resultsOne hundred and five adults (75.2% female, mean age 44.9 years) with overweight or obesity were included in the analyses. These participants represent a subsample of participants in a larger randomized controlled trial (NCT01500356). A resting pseudo-continuous arterial spin labeling (pCASL) scan was acquired to examine rCBF. Age, sex, and BMI were included as covariates. At baseline, A carriers had greater rCBF in a diffuse cluster extending into the brainstem, motor cortex, and occipital lobe, but lower perfusion in the temporal lobe. We found no evidence that FTO moderated the effect of the intervention group assignment on rCBF changes.ConclusionOverall, these results indicate that (a) individual variation in rCBF within a sample with overweight and obesity may be attributed to a common FTO variant, but (b) a weight loss intervention is effective at increasing rCBF, regardless of FTO genotype.

Association of rs1137101 with hypertension and type 2 diabetes mellitus of Mongolian and Han Chinese.

BACKGROUNDHypertension (HTN) and type 2 diabetes mellitus (T2DM) are often coincident, and each condition is considered a risk factor for the other. Both occur frequently in the Inner Mongolia region of China. The reasons for differences in risk between Han and Mongolian ethnic groups are not known. The LEPR gene and its polymorphism, rs1137101 (Gln223Arg), are both considered risk factors for HTN and T2DM, but any role of rs1137101 in the occurrence of HTN + T2DM remains unclear for Mongolian and Han populations in the Inner Mongolia region.AIMTo investigate the relationship between rs1137101 and the occurrence of HTN with T2DM in Mongolian and Han populations in Inner Mongolia.METHODSA total of 2652 subjects of Han and Mongolian ethnic origins were enrolled in the current study, including 908 healthy controls, 1061 HTN patients and 683 HTN patients with T2DM.RESULTSThe association between the rs1137101 polymorphism and HTN with T2DM was analyzed, and differences between Han and Mongolian individuals assessed. There was a significant correlation between rs1137101 and HTN (co-dominant, dominant, over-dominant and log-additive models) and HTN + T2DM (co-dominant, dominant, over-dominant and log-additive models) after adjustment for sex and age in individuals of Mongolian origin. rs1137101 was significantly associated with HTN (co-dominant, recessive and log-additive models) and HTN + T2DM (co-dominant, dominant, over-dominant and log-additive models) in the Han Chinese population.CONCLUSIONMongolian and Han subjects from Inner Mongolia with HTN who had rs1137101 were protected against the development of T2DM. Allele A has the opposite impact on the occurrence of HTN in Mongolian and Han Chinese populations.

Analysis of the association of FTO, PPARG and PPARGC1A gene polymorphisms with carbohydrate metabolism disorders

Background. Conducting molecular and genetic studies to investigate susceptibility to multifactorial and polygenic diseases, such as type 2 diabetes melitus and pre-diabetic conditions, is of great importance for the development of personalized prevention programs and the choice of optimal treatment. Taking into account regional and ethnic features, the study of polymorphic markers of candidate genes for fat and carbohydrate metabolism has a great practical value.&#x0D; Aim. To investigate associations of polymorphisms of the FTO rs9939609, PPARG rs180128, PPARGC1A rs8192678 genes with the risk of developing type 2 diabetes mellitus and pre-diabetic conditions in residents of the Republic of Tatarstan.&#x0D; Material and methods. An observational single-stage single-center controlled study was conducted in patients with various disorders of carbohydrate metabolism: prediabetes (n=138) and a confirmed diagnosis of type 2 diabetes mellitus (n=134). Molecular genetic analysis of rs9939609 polymorphism of the FTO gene, rs8192678 polymorphism of the PPARGC1A gene and rs1801282 polymorphism of the PPARG gene was performed using real-time polymerase chain reaction. The distribution of patient genotypes and alleles was compared with the Russian population. Statistical data processing included nonparametric correlation analysis using Pearsons coefficient, calculation of Student's and 2 tests, odds ratios, arithmetic mean values and their standard deviations using GraphPad InStat software.&#x0D; Results. The A allele of the rs9939609 polymorphism of FTO gene increases the risk of developing type 2 diabetes mellitus and early carbohydrate metabolism disorders (OR=2.73, p=0.00007 and OR=4.17; p=0.00002, respectively). The GG genotype of the rs180128 polymorphism of the PPARG gene is associated with the risk of type 2 diabetes mellitus (OR=2.77, p=0.02).&#x0D; Conclusion. The expected association of the rs9939609 FTO polymorphic marker, which determines the development of insulin resistance, with the development of type 2 diabetes mellitus and the presence of early carbohydrate metabolism disorders was obtained.

Development of a genetic risk score for obesity predisposition evaluation.

Obesity is a major public health issue resulting from an interaction between genetic and environmental factors. Genetic risk scores (GRSs) are useful to summarize the effects of many genetic variants on obesity risk. In this study, we aimed to assess the association of previously well-studied genetic variants with obesity and develop a genetic risk score to anticipate the risk of obesity development in the Iranian population. Among 968 participants, 599 (61.88%) were obese, and 369 (38.12%) were considered control samples. After genotyping, an initial screening of 16 variants associated with body mass index (BMI) was performed utilizing a general linear model (p < 0.25), and seven genetic variants were selected. The association of these variants with obesity was examined using a multivariate logistic regression model (p < 0.05), and finally, five variants were found to be significantly associated with obesity. Two gene score models (weighted and unweighted), including these five loci, were constructed. To compare the discriminative power of the models, the area under the curve was calculated using tenfold internal cross-validation. Among the studied variants, ADRB3 rs4994, FTO rs9939609, ADRB2 rs1042714, IL6 rs1800795, and MTHFR rs1801133 polymorphisms were significantly associated with obesity in the Iranian population. Both of the constructed models were significantly associated with BMI (p < 0.05) and the area under the mean curve of the weighted GRS and unweighted GRS were 70.22% ± 0.05 and 70.19% ± 0.05, respectively. Both GRSs proved to predict obesity and could potentially be utilized as genetic tools to assess the obesity predisposition in the Iranian population. Also, among the studied variants, ADRB3 rs4994 and FTO rs9939609 polymorphisms have the highest impacts on the risk of obesity.