CC Genotype Research Articles

Meta-analysis and systematic review for the genetic basis of cleft lip and palate.

Cleft lip and palate (CLP) are a usually inherited anomaly described as a gap in the oral cavity's upper lip and/or roof. The etiology of CLP involves both genetic and environmental factors. The current study aimed to examine the genetic basis of nonsyndromic (NS) CLP (NSCL/P) and its association with specific genetic polymorphisms. We conducted a meta-analysis and systematic review of seven articles, which provided information on the correlation between genes and NSCL/P risk. Our results proved that the MTHFR c.677C>T polymorphism was correlated with the risk of NSCL/P, favoring the control group in the CC genotype and the cases group in the CT genotype. The TT genotype favored the control group. Additionally, the MTHFD1 1958G>A polymorphism was correlated with the high NSCL/P risk in children. However, the MTHFR C677T polymorphism did not show a significant correlation with NSCL/P risk in the analysis, although it was correlated with the high risk in specific populations. These results contribute to our knowledge about the genetic causes of NSCL/P and highlight the importance of specific genetic polymorphisms in its development. Further research is needed to explore the genetic mechanisms underlying NSCL/P in different populations and to elucidate its implications for diagnosis, treatment, and prevention strategies.

LncRNA RNF144A-AS1 gene polymorphisms and their influence on lung cancer patients in the Chinese Han Population

Lung cancer is primarily classified as NSCLC, which is distinguished by a wide range of genetic variations. This study focused on RNF144A-AS1, a relatively unexplored lncRNA, to explore the impact of its genetic polymorphisms on the susceptibility to NSCLC. We detected RNF144A-AS1 expression and its correlation with prognosis and clinical pathological features using bioinformatics analysis. The association between RNF144A-AS1 polymorphism and NSCLC susceptibility was evaluated using case-control methods. This investigation featured a cohort of 700 NSCLC individuals and 700 healthy controls. The genotype of genetic variation was detected by PCR-RFLP and iMLDR, followed by subsequent calculation of OR and 95 % CI. Our data show that RNF144A-AS1 exhibits high expression levels in LUAD tissues and its expression is closely linked to LUAD progression and prognosis. Carrier of RNF144A-AS1 rs3806609 TT genotype increased NSCLC susceptibility compared to carrier of rs3806609 CC genotype (OR=2.21, 95%CI=1.57-3.13). Our study identifies RNF144A-AS1 genetic variants as potential susceptibility markers in NSCLC. RNF144A-AS1 promotes cell proliferation and migration in LUAD through the IFN-γ/JAK2/STAT1 signalling pathway. Collectively, these findings pave the way for developing targeted therapies and diagnostic tools based on RNF144A-AS1 and its variants.

Dairy intake and cognitive function in older adults in three cohorts: a mendelian randomization study.

Meta-analyses of observational studies on the effect of dairy on cognitive function have yielded inconclusive results, potentially due to unmeasured confounding. To avoid the no-unmeasured confounding assumption, we used lactase persistence genetic variant as an instrumental variable, for which the CC genotype is associated with lower lactase production and, consequently, lower dairy consumption. We used it to assess the effect of long-term consumption of total and non-fermented dairy on cognitive function. We included 43,836 individuals over 55 years old with genotyping, dietary data, and cognitive function measurements from three population-based studies: CoLaus|PsyCoLaus (Switzerland), the Rotterdam Study (the Netherlands) and the Canadian Longitudinal Study on Aging (CLSA - Canada). We performed a one-sample Mendelian randomization using two-stage least-squares regression. First, we estimated total and non-fermented dairy consumption by T-allele frequency. Second, we used the estimated dairy consumption in linear regression models on general cognition, assessed by the Mini-Mental State Examination (MMSE) and the Mental Alternation Test, executive function, verbal fluency, verbal learning, and memory. Per T-allele, total dairy intake and non-fermented was 24.8 and 15.3g/day higher in PsyCoLaus, 57.9 and 49.8g/day in the Rotterdam Study, and 0.31 and 0.29 times/day in CLSA, respectively. We found no association between the genetically predicted difference and the MMSE in PsyCoLaus and the Rotterdam Study. However, lactase persistent individuals scored 3.4 (95% CI2.1- 4.7) and 3.5 (95% CI 2.3-4.7) points more in the Mental Alternation Test for total and fermented dairy, respectively, in CLSA. Similarly, lactase persistent participants in CLSA had higher verbal fluency, verbal learning and executive function, but no differences were found in the other cohorts. Such inconsistencies might stem from different FFQs across cohorts and consumption ranges. Nonetheless, the generally small magnitude of effect sizes may suggest that there is no real effect between total or non-fermented dairy intake and cognitive function. The evidence for a causal effect of dairy consumption on general cognitive function is weak, consistent with previous results from classic analysis from observational studies. Interventions targeting dairy are unlikely to have a relevant effect on cognitive function.

Serotonin Receptors Polymorphisms Are Associated With Cyclic Vomiting Syndrome.

Cyclic vomiting syndrome (CVS) is a disorder characterized by sudden, recurrent episodes of severe nausea and vomiting. The pathophysiology of CVS is not known but genetic factors that regulate emetic neurocircuitry have been proposed. The aim of this study was to investigate whether different variations in genes encoding serotonin receptors (HTRs) are associated with susceptibility to CVS and/or CVS symptoms. This case-control study included 70 patients with CVS:16 male and 54 female, and 2504 healthy controls from the 1000 Genomes Project database. Single-nucleotide polymorphisms (SNPs) in genes encoding serotonin receptors (HTR1B, HTR1D, HTR3B and HTR3C) and correlations between SNPs and the symptoms of CVS were determined. Our study discovered that patients with GG, AA and GG genotypes of HTR1B/D rs6296, rs6298 and rs6300, respectively, as well as the CC genotype of HTR3B rs176744 are associated with an increased risk (p < 0.001), whereas allele C in rs3788987 (HTR3B, p < 0.01) and allele A in rs6766410 (HTR3C, p < 0.05) were associated with a decreased risk of CVS. In addition, statistical analysis indicated that CVS patients with GA or AA genotypes of HTR1D rs676643 gene have a seven-fold increase in risk of depression compared to patients with GG genotype (p < 0.01). Our study revealed for the first time that variations in 5-HTR genes may contribute to CVS susceptibility and CVS-related symptoms.

CC genotype at TCF7L2 diabetes risk locus rs7903146 directs a coordinated fatty acid response to a Mediterranean diet intervention: a randomized controlled trial.

Previous studies identified genetic links between the TCF7L2 C/T variant rs7903146, type 2 diabetes (T2D), and obesity. We wished to deepen our understanding of how specific diets interact with this variant to affect blood metabolites, an aspect not previously investigated. Hence, we conducted a controlled study where individuals with different genotypes followed a Mediterranean (Med) or low-fat (LF) diet for one week. Participants were recruited from the Boston, MA (USA) area. Anthropometric and clinical measures were taken. Genotypes at rs7903146 were ascertained, with homozygous carriers of the more common and protective CC or risk TT genotype invited to participate. Participants followed both diets (LF or Med) for one week with ~10 days' washout between diets. Blood samples taken at the beginning and end of each diet period underwent metabolomics analysis using nuclear magnetic resonance spectroscopy. We evaluated how the diet affected different metabolites based on genetic profile. The cohort of 35 persons was 43% female, aged 18 to 70 y, with BMI between 26.4 to 33.9 kg/m2. Focusing on fatty acids (FAs) and other lipid metabolic factors (n = 23), we observed a greater number and stronger correlations among these factors in the CC genotype-Med diet group than the other three genotype-diet combinations. An aggregate of 11 factors, each negatively correlating with delta saturated fatty acids (SFA), showed a significant genotype-Med diet interaction on delta-SFA in CC individuals on the Med diet (p = 0.0046). A similar genotype-Med diet interaction was observed for delta-monounsaturated fatty acids (MUFA) (p = 0.0078). These interactions were not statistically significant at the end of the LF intervention. Our findings suggest that the Mediterranean diet has stronger influence on regulating lipid factors in individuals with the CC genotype at TCF7L2 variant rs7903146. This diet-genotype interaction may have significant implications for understanding the inter-individual variation of metabolic response on specific dietary regimens.

АССОЦИАЦИЯ ПОЛИМОРФНЫХ ВАРИАНТОВ ГЕНА CAPN1 С ЖИВОЙ МАССОЙ У ОВЕЦ КАЛМЫЦКОЙ КУРДЮЧНОЙ ПОРОДЫ И ЕЕ ПОМЕСЕЙ С ПОРОДАМИ ШАРОЛЕ И ДОРПЕР

The purpose of research is to study the phenotypic effect of genotypes of the polymorphic calpain gene (CAPN1) on live weight in Kalmyk fat-tailed sheep and their crosses with the Charolais and Dorper breeds to substantiate the possibility of genetic marking of productivity at an early age. Objectives – carrying out genotyping and accounting of productivity indicators of animals of the Kalmyk fat-tailed breed (KK), Charolais (Sh), Dorper-Kalmyk crossbred ewes (½D×½KK), obtained purebred and crossbred young animals; establishing the influence of genotypes for the CAPN1 gene on live weight and average daily gain. It was found that in Kalmyk fat-tailed and Charolais breeding rams, carriers of the C allele in the CAPN1 gene were more often detected, while among purebred and crossbred ewes the occurrence of the C and T alleles was equal. In purebred young animals and ½ Sh ×½KK crosses, individuals with the T allele predominated; in ½ Sh ×¼D×¼KK crossbreeds, the carriers of the C allele predominated. Population genetic analysis in none of the groups did not reveal significant differences in the observed genotype frequencies from those theoretically expected at Hardy-Weinberg equilibrium. Regardless of breed and sex, the live weight of young animals at birth of different genotypes for the CAPN1 gene was similar, while at four months of age, both rams and lambs with the CC genotype had a significant superiority over their peers of other genotypes. In purebred rams, the greatest difference was observed between animals of the CC and ST genotypes, in crossbreeds ½ Sh ×½KK – animals of the CC and TT genotypes, which amounted to 10.4 and 8.1 %; 9.94 and 10.95 % (p &lt; 0.05), respectively. Among the females, the greatest differences were observed during purebred breeding between animals of the CC and TT genotypes – 15.6 and 16.6 % (p &lt; 0.05), respectively.

Association of LPCAT1-rs8352 genetic variant with susceptibility and severity of pediatric bronchial asthma: a case-control study

BackgroundThis study aimed to investigate the possible association of LPCAT1-rs8352 genetic variant (single nucleotide change C to G) with the onset and severity of pediatric asthma. Additionally, the study examined the influence of LPCAT1-rs8352 genotypes on asthma-related biomarkers including blood eosinophils count (BEC), eosinophil cationic protein (ECP), high-sensitivity C-reactive protein (hs-CRP), and immunoglobulin E (IgE) and on lung function [forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC)].Patients and methodsThe study included ninety-six participant grouped into two groups: G1 (46 asthmatics) and G2 (50 healthy controls). ECP, hs-CRP, and total IgE serum levels were measured using their corresponding ELISA kits. Neonatal blood DNA was extracted using the Gene JET™ Whole Blood Genomic DNA Purification Mini Kit. Genotyping was performed by RT-PCR.ResultsA significantly higher proportion of individuals in G1 had the LPCAT1-rs8352 CC and GC genotypes compared to G2 (p < 0.001). Individuals with the CC genotype exhibited significantly more severe asthma, along with elevated levels of BEC, ECP, hs-CRP, and total IgE. Those with the GC genotype demonstrated a similar, though less severe, pattern, followed by individuals with the GG genotype. The FEV1 and FVC values showed the opposite trend, with individuals having the GG genotype exhibiting the highest lung function values.ConclusionThe LPCAT1-rs8352 allele C is associated with pediatric asthma onset and severity. Further research on the LPCAT1 genetic variants may provide a deeper understanding of pediatric bronchial asthma mechanisms and lead to improved management strategies.

ВЛИЯНИЕ ГЕНА ЛЕПТИНА НА ПРОДОЛЖИТЕЛЬНОСТЬ ХОЗЯЙСТВЕННОГО ИСПОЛЬЗОВАНИЯ КРУПНОГО РОГАТОГО СКОТА

The purpose of research is to study, systematize and summarize the available scientific data on the effect of the leptin gene on the duration of economic use of cattle over the past ten years. This paper presents the results of scientific research on the effect of polymorphisms A80V, Y7F and R25C on the duration of use of animals in agriculture. Polymorphisms R25C and Y7F occur in the second, and A80V – in the third exon of the leptin gene. Research has linked the R25C site to milk protein content, milk fat content, calving ease, and pregnancy duration. The CC genotype is associated with a greater risk of culling in cows. The Y7F site is associated with animal viability, and the FF genotype has a higher risk of culling. The LEP-A80V site affects the duration of animal management and the level of profitability. Cows with the VV genotype have a higher risk of culling than cows with the AA genotype. Assessment of the influence of the leptin gene must be carried out comprehensively across all loci, and not just one. Assessing the combined effect of a gene at three loci allows for a more refined analysis of the animal’s potential. Studies show that the YY genotype predominates at the Y7F site, and genotypes with the F allele are washed out of the population. Most often in domestic farms, the heterozygous genotype of the R25C site is found, but the RR genotype has a positive effect on the longevity of animals. Genotypes AA and AV are more common on the A80V site, the frequency of occurrence of the unfavorable genotype VV is lower. Thus, studying the effect of leptin gene polymorphisms on the economic use of cattle is an important area of scientific research in agriculture. Research results make it possible to predict the duration of use of animals and increase the profitability of agricultural enterprises.

The Association of Genetic Variants Within the Type XII Collagen and Tenascin C Genes with Knee Joint Laxity Measurements

Background/Objectives: Types I, V, and XI collagen gene variants have been reported to associate with measurements of knee joint laxity and/or absolute knee ligament length changes. Type XII collagen and tenascin C are also ligament structural proteins whose expression is regulated by mechanical loading. This study investigated whether COL12A1 and TNC variants are associated with knee laxity and/or ligament length changes. Methods: Genu recurvatum, anterior–posterior tibial translation, external–internal tibial rotation, and ligament length changes were measured in 128 healthy participants. They were genotyped for COL12A1 (rs970547) and TNC (rs1061494, rs2104772, rs1138545). Results: Both the COL12A1 AA and TNC rs1061494 TT genotypes were associated with decreased external (p = 0.007, p = 0.010) and internal (p = 0.025, p = 0.002) rotation, as well as slack (p = 0.033, p = 0.014), in the dominant leg. Both genotypes, together with sex, weight, and/or COL1A1 genotypes, explained 26% and 32% of the variance in external and internal rotation, respectively. The TNC genotype, sex, and BMI explained 23% of the variance in slack. The COL12A1 AA and the TNC rs1061494 TT genotypes were associated with smaller changes in the MCL (aMCL: COL12A1 p = 0.009, TNC p = 0.045; iMCL: COL12A1 p = 0.004, TNC p = 0.043; pMCL: COL12A1 p = 0.003, TNC p = 0.067; aDMCL: COL12A1 p = 0.007, TNC p = 0.020; pDMCL: COL12A1 p = 0.007, TNC p = 0.023) and/or LCL (COL12A1 p = 0.652, TNC p = 0.049) lengths within the dominant knee. The TNC rs1061494 CC genotype was associated with larger changes in the non-dominant anterior (p = 0.021) and posterior (p &lt; 0.001) ACL bundle lengths. Conclusions: These findings suggest that COL12A1 and TNC variants are associated with internal–external tibial rotation and knee ligament length changes in healthy individuals.

Genetic Polymorphism of Zinc Transporter-8 Gene (SLC30A8), Serum Zinc Concentrations, and Proteome Profiles Related to Type 2 Diabetes in Elderly

Background and Aims: Older adults are particularly susceptible to type 2 diabetes mellitus (T2DM) due to factors such as age-related insulin resistance, decreased physical activity, and deficiency of micronutrients, especially zinc. Studies have suggested that the risk allele of the zinc transporter 8 gene (SLC30A8) single-nucleotide poly-morphism (SNP) rs13266634 may contribute to T2DM susceptibility in addition to the complex protein interactions and alterations in the protein expressions and modifications associated with T2DM. This study was implemented to study the associations between SLC30A8 polymorphism, serum zinc levels, and the profiles of proteins differentially expressed in nondiabetic (n = 116) and prediabetic/diabetic (n = 149) subjects. Methods: SNP genotyping using TaqMan® assay and proteomic analysis by LC-MS/MS were performed in each group. Results: The results showed a higher risk of diabetes in individuals with the risk genotype CC accompanied by a low serum zinc level than in those with other genotypes. Profiles of proteins differentially expressed between the groups were identified and shown to be particularly associated with zinc-related functions, zinc transporter 8, and glucose metabolism. Proteins exclusively expressed in prediabetes/diabetes were assigned to a Reactome pathway related to zinc transporter and insulin processing. Conclusions: Our findings suggest that individuals carrying at least one copy of SLC30A8 rs13266634 accompanied by a low serum zinc level might be susceptible to T2DM, which could be due to alterations in insulin signaling and zinc metabolism. Understanding this relationship deepens our understanding of the genetic and molecular mechanisms underlying T2DM risk, offering potential targets for therapeutic intervention and prevention strategies.

Impact of ABO gene polymorphism and von Willebrand factor on genetic susceptibility to acute lymphoblastic leukemia in Egyptian pediatric patients

BackgroundAcute lymphoblastic leukemia (ALL) is the most common malignancy affecting children. The ABO blood group system and von Willebrand factor (VWF) have been associated with altering cancer risk, but few studies have examined their relationship with pediatric ALL. This study investigated the association between ABO gene polymorphism, VWF levels, ABO blood groups, and ALL risk in Egyptian pediatric patients.MethodsSeventy-two ALL patients and 36 healthy controls were ABO phenotyped and genotyped for the ABO rs2519093 polymorphism using PCR–RFLP. VWF antigen levels were measured by ELISA.ResultsThe CC genotype and C allele frequencies were significantly higher in ALL patients compared to controls (p < 0.001) and increased ALL risk by 12.94-fold and 7.63-fold, respectively. VWF levels were significantly higher in ALL patients versus controls overall (p = 0.006) and in the A, B, and O blood groups individually. After adjusting for VWF levels, the O, A, and B blood groups increased ALL risk 87.95-fold, 15.95-fold, and 8.77-fold, respectively, compared to AB.ConclusionThe ABO C allele and O, A, and B blood groups are associated with increased pediatric ALL susceptibility in Egyptian patients, potentially through elevated VWF levels. These findings highlight ABO gene polymorphisms and blood groups as possible risk factors for ALL development.

5,10-methylenetetrahydrofolate reductase C677T gene polymorphism as a risk factor for premature coronary artery disease in patients with type 2 diabetes mellitus

BackgroundAfrica, like the rest of the world, is experiencing an increasing prevalence of diabetes mellitus. Diabetes increases the risk for coronary artery disease (CAD) by fourfold compared to people without diabetes. C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR) and hyperhomocysteinemia were reported by many studies as risk factors for CAD among patients with type 2 diabetes mellitus (T2DM). Early detection of modifiable risk factors for CAD is an important aspect of management of diabetes. This is the only study in Sudan which investigates the association between MTHFR genotypes and plasma homocysteine levels, and their role in premature CAD (PCAD) among patients with T2DM.MethodsThis study is a comparative study. We enrolled 226 Sudanese patients with T2DM, age range 25-60 years, recruited from Alshaab and Omdurman teaching hospitals in Khartoum State. 113 patients had CAD confirmed by angiography and electrocardiography (ECG) and 113 had no evidence of CAD. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP), using Hinf1 restriction enzyme, were used to determine MTHFR genotypes. Plasma homocysteine levels were determined by enzymatic assay on the Hitachi Cobas Integra® 400 plus. Data was analyzed using statistical package for Social Sciences (SPSS) 23, using Mann-Whtney U test, general linear model, Chi-square test and logistic regression analysis.ResultsThe frequencies of TT, CT, and CC genotypes were 16,40 and 44% among T2DM patients with PCAD. In T2DM patients without PCAD, the frequencies of TT, CT, and CC genotypes were 00,19 and 83%. The T allele showed strong association with PCAD among T2DM patients, p &amp;lt;0.001, odds ratio (OR) 6.2, 95% CI (3.4-11.6). Patients with PCAD showed higher plasma homocysteine levels than patients without PCAD (13.5 µmol/L versus 10 µmol/L, p &amp;lt; 0.001). The T allele had significant effect on homocysteine level, (p &amp;lt;0.001). Plasma homocysteine levels were higher in individuals with TT genotype than those with CT or CC genotypes in patients with PCAD (16.2 + 5.3, 14.3 + 5.7 and 12.9 + 5.02 µmol/L, p=0.017). Homocysteine levels showed a significant association with CAD, p&amp;lt;0.001, OR 3.2, 95% CI (1.9—5.5).ConclusionsOur study suggests that C677T polymorphism of MTHFR gene and hyperhomocysteinemia are risk factors for PCAD in Sudanese population with T2DM.

ЭЛЕМЕНТНЫЙ СТАТУС ЖИВОТНЫХ И ЕГО РАСПРЕДЕЛЕНИЕ В СРЕДЕ ТЕЛОК С РАЗЛИЧНЫМ АЛЛЕЛЬНЫМ НАБОРОМ ГЕНОВ, АССОЦИИРОВАННЫХ С КАЧЕСТВОМ ГОВЯДИНЫ

The purpose of the study is to determine the effect of polymorphism of the CAPN1 and TG5 genes on the elemental status of heifers in the conditions of the technogenic zone of the Southern Urals. The study was conducted at Sovkhoz Bredinsky LLC, Chelyabinsk Region, on 40 heads of Simmental Bredinsky meat-type heifers. Laboratory studies were carried out at the Center for Collective Use of the Federal State Budgetary Scientific Institution of the Federal Scientific Center of the BST RAS. According to the results of genotyping, biosubstrates in the form of wool were taken from animals of different genotypes and sent to Mikronutrienty LLC (Moscow), where their elemental composition was determined by mass spectrometry using a Nexion 300D quadrupole mass spectrometer (Perkin Elmer, USA). The results indicate a moderate heterogeneity of the genotyped population for the CAPN1 gene and a significant shift in heterozygosity for the TG5 gene. The elemental status of the animals is reflected in a graph that does not show any excess of toxic elements of the upper limits of the reference values for the Southern Urals zone, with the exception of the excess of the upper centiles of the reference norms for some essential elements, such as Mg (265.3 µg/g), K (2840.7) and Na (1571.6 µg/g), which is associated with the peculiarities of the geochemical conditions of the area. The results of the analysis of the distribution of the content of elements in the hair of 15–16-month-old heifers, depending on the polymorphism of the CAPN1 and TG5 genes, showed the lack of reliability of the dependence of the content of elements in the hair of animals on the genotype according to the polymorphic state of the above genes. At the same time, some peculiarities in the distribution of magnesium were observed for the TG5 gene, the amount of which in animals with the TT genotype was 2.1 times less than in analogues with the CC genotype, and for zinc, on the contrary, it was 33.2 % more (P &gt; 0.05). To obtain reliable values, it is necessary to repeat the studies on a larger sample.

The correlation between miR-21 single nucleotide polymorphisms and the susceptibility of non-small cell lung cancer

BackgroundThere are still gaps in the study of the miRNA and its SNPs in some diseases such as non-small cell lung cancer (NSCLC). The study aimed to provide useful information on the treatment of NSCLC by investigating the association between miR-21 and its SNPs and NSCLC susceptibility.MethodsThe serum of NSCLC patients (n = 205) and cancer-free controls (n = 217) were collected in this study for RNA extraction. The qRT-PCR was used to evaluate the expression of miR-21 and Taqman qPCR was used for genotyping and quantifying miR-21 SNPs (rs1292037, rs6504593). The association of the expression of miR-21, the miR-21 SNPs and their interactions with the susceptibility of NSCLC patients were analysed using logistic regression analysis in this study.ResultsThis study showed that the overexpression of miR-21 was related to NSCLC. The C allele and CC genotypes of rs1292037 and rs6504593 were associated with the increased risk of NSCLC susceptibility. Moreover, the interactions of rs1292037 and rs6504593 were also a risk factor for NSCLC. The CC genotypes of rs1292037 and rs6504593 were associated with the increase of miR-21 expression.ConclusionThe overexpression of miR-21, the miR-21 SNPs rs1292037 and rs6504593 and their interactions were associated with NSCLC susceptibility. MiR-21 and its SNPs have potential for being targets in the therapy of NSCLC. This study provided important information for the treatment of NSCLC.

Genetic Polymorphisms in HMGCS1 Gene and Its Association with Slaughter Characteristics, Meat Quality, and Organ Coefficients in Guizhou White Goats.

This study aimed to identify polymorphisms in the gene encoding the 3-hydroxy-3-methylglutaryl-CoA synthase 1, HMGCS1, and analyze their association with slaughter characteristics, meat quality, and organ coefficients in Guizhou white goats. A total of 153 twelve-month-old Guizhou white goats (78 male and 75 female) were included in the study. Slaughter characteristics, meat quality, and organ coefficients were assessed. Association analyses between genotypes and phenotypic traits were conducted using a generalized linear model. Four polymorphic loci were identified, i.e., g.15523T>C, g.15530G>C, g.18413T>C, g.19711G>A in exons 5, 8, and 9 of the HMGCS1 gene. Across all polymorphic loci, males of the same genotype generally exhibited significantly better slaughter traits compared to females of the same genotype (p < 0.05). At the g.18413T>C locus, differences in shear force were observed between males and females of the same genotype and within the same sex across different genotypes (p < 0.05). Organ coefficients were significantly higher in males of the same genotype compared to females (p < 0.05). The g.15523T>C and g.15530G>C loci were found in strong linkage disequilibrium and significantly associated with intramuscular fat content (p < 0.05). Fat content in diploid Hap2/2 individuals was significantly higher than in Hap1/1 and Hap1/2 (p < 0.05). At the g.19711G>A locus, female goats with the CC genotype showed significantly higher levels of dry matter compared to male goats of the same genotype and female goats of other genotypes within the group. Organ coefficients for the liver and hooves in male goats were significantly higher than in females of the same genotype (p < 0.05). The strongly linked loci g.15523T>C and g.15530G>C were significantly associated with intramuscular fat content and could be used as molecular markers for enhancing this trait in goat breeding programs, fostering the development of goat production.

The impact of the interaction between BDNF rs7103411 gene polymorphism and social activities on mild cognitive impairment in community-dwelling elderly adults.

To investigate the correlation between BDNF gene polymorphism, BDNF levels, and susceptibility to mild cognitive impairment (MCI). In this study, we investigated 107 elderly adults individuals from a community in Zhongshan, Guangdong Province, with an average age of 73.17 ± 7.081 years. The participants included 52 patients with Mild Cognitive Impairment due to Alzheimer's Disease and 55 cognitively normal elderly adults control subjects. The two groups were matched based on gender, age, and education level. We assessed their cognitive functions and analyzed their genotypes and serum BDNF levels. Analysis of covariance (ANCOVA) was used to evaluate the differences in serum BDNF levels between the MCI group and the control group. Multivariate linear regression was utilized to analyze the association between BDNF levels and susceptibility to MCI, as well as cognitive functions. Multivariate logistic regression was employed to investigate the association between BDNF gene polymorphisms and the risk of developing MCI, along with their interactions. The ANCOVA analysis indicated that there was no significant difference in serum BDNF levels between the MCI group and the control group (P > 0.05). Correlation analysis revealed a negative correlation between Mini-Mental Status Examination (MMSE) total scores and MCI (r = -0.461, P = 0.001), with significant correlations observed in orientation (r = -0.420, P = 0.002). Multiple linear regression analysis showed that specific polymorphisms, including rs7103411 (CT+TT vs. CC), rs6265 (CT and CT+TT vs. CC), rs11030104 (AG and AG+GG vs. AA), and rs988748 (CG+CC vs. GG), were significantly associated with decreased serum BDNF levels (P < 0.05). Multivariate logistic regression showed that rs7103411 polymorphism was associated with susceptibility to MCI; individuals with the CT or CC genotype had a 0.370 times lower risk of developing MCI compared to those with the TT genotype (OR = 0.370, 95% CI: 0.141-0.970, P = 0.043). A significant interaction was found between rs7103411 and social activity, which influenced the risk of developing MCI. Specifically, individuals with the CT or TT genotype of rs7103411 who engaged in social activities had a significantly lower risk of developing MCI (OR = 0.32, 95% CI: 0.117-0.878, P = 0.027). This study indicates that BDNF rs7103411、rs6265、rs11030104 and rs988748 are associated with decreased serum BDNF levels in MCI patients. Individuals carrying the TT genotype in the BDNF rs7103411 gene are associated with an increased susceptibility to MCI. Individuals with the rs7103411 CT or TT genotype who participated in social activities showed a significantly reduced risk of developing MCI, suggesting that the interaction between the BDNF rs7103411 genotype and social activity can help reduce the risk of MCI.

The relationship between gallstone disease and the genetic variants of the sterol transporter adenosine triphosphate–binding cassette G8 and G5 in Egyptians

BackgroundGallstones are abnormal lumps in the gallbladder or biliary tract due impaired cholesterol, bilirubin, or bile salt metabolism. The Adenosine triphosphate binding cassette transporter genes G5 and G8 (ABCG5, ABCG8) are two half transporters which work together as a heterodimer to regulate cholesterol levels in bile, and any alterations in their function can contribute to gallstone formation. The primary objective of this study was to evaluate the association between three specific polymorphisms—ABCG5 i7892T > C, ABCG5 Q604E, and ABCG8 D19H—and the risk of gallstone disease (GSD) in Egyptian females. These polymorphisms result from nucleotide substitutions in the gene sequences, which affect the transporter’s ability to efficiently regulate cholesterol secretion into the bile. This alteration can lead to cholesterol supersaturation in the bile, a key factor in the development of cholesterol gallstones. Additionally, the study aimed to examine the impact of these genetic variations on serum lipid profile to understand their role in modulating biochemical markers associated with GSD. Furthermore, the study sought to investigate haplotype patterns and explore their combined effects on disease susceptibility, providing deeper insight into the genetic factors that contribute to the development of GSD.MethodsThe study included 100 female patients diagnosed with gallstones and 100 healthy controls. Genotyping of single nucleotide polymorphisms (SNPs) was performed using allelic discrimination pre-designed TaqMan polymerase chain reaction method. Various laboratory investigations were measured using enzymatic colorimetric methods, and hematology analyzer was used for the whole blood count test.ResultsBetween patients with gallstone disease and healthy controls, there were statistically significant differences in the distribution of these genes polymorphisms. Q604E CC genotype (OR = 15.2; P = 0.004) and C allele (OR = 2; P = 0.007) in ABCG5 (rs6720173) as well as D19H GC genotype (OR = 2.9; P = 0.002) and C allele (OR = 2; P = 0.004) in ABCG8 (rs11887534) were significantly more frequent in gallstone patients. The CCC haplotype is a statistically significant predictor of GSD.ConclusionsThis study suggests that ABCG8 D19H (G/C) and ABCG5 Q604E (C/C) genotypes may play a significant role in GSD susceptibility among Egyptian females.Graphical abstract

AMPD1 and MTHFR genes are not associated with calcium levels in rheumatoid arthritis patients with methotrexate therapy in Indonesia

Rheumatoid Arthritis (RA) is a chronic and progressive autoimmune disease that affects synovial tissues has greater risk of developing secondary osteoporosis (OP). In particular, polymorphisms in Adenosine Monophosphate Deaminase 1 (AMPD1) and Methylenetetrahydrofolate Reductase (MTHFR) affect the outcome of methotrexate (MTX) treatment in patients with RA. Therefore, this study aimed to determine the association of AMPD1 rs17602729, MTHFR C677T, and MTHFR A1298C polymorphisms with MTX activity in RA patients. A retrospective design was adopted to collect data from medical records and blood samples of 99 patients experiencing outpatient care at a referral hospital in Bandung. The inclusion criteria were patients diagnosed with RA, aged 18–59 years, and receiving MTX therapy for ≥ 6 months. DNA was isolated and then amplified using Polymerase Chain Reaction (PCR), and genotyping was performed with Sanger sequencing. The kinetic photometric method was used to measure the levels of calcium in the samples. The results showed that there is no significant association between the MTHFR C677T genotype variant or allele with calcium levels, as indicated by p-values of 0.177 and 0.174, respectively. The association between the MTHFR A1298C genotype variant or alleles with calcium levels was also not significant (p = 0.206 and p = 0.090, respectively). However, most patients had normal calcium levels (76 patients; 77.6%) with the MTHFR C677T genotype variant CC and the MTHFR A1298C genotype variant AA (84 patients; 84.9%). AMPD1 rs17602729 in all patients had a CC genotype with normal calcium levels. The results suggested that there was no significant association between the genetic variation of AMPD1 rs17602729, MTHFR C677T, and MTHFR A1298C with serum calcium levels in patients with RA receiving MTX therapy.

Comparative efficacy and safety of sitagliptin or gliclazide combined with metformin in treatment-naive patients with type 2 diabetes: A single-center, prospective, randomized, controlled, noninferiority study with genetic polymorphism analysis.

This study evaluates the efficacy and safety of sitagliptin versus gliclazide, combined with metformin, in treatment-naive patients with type 2 diabetes mellitus (T2DM) and glucotoxicity. In this single-center, randomized, controlled noninferiority trial, 129 treatment-naive patients with T2DM with glucotoxicity (fasting plasma glucose [FPG] ≥ 200 mg/dL and glycated hemoglobin ≥ 9.0%) were randomized to receive sitagliptin plus metformin (n = 66) or gliclazide plus metformin (n = 63) for 12 weeks. Sitagliptin and gliclazide were given for the first 4 weeks, followed by metformin monotherapy for 8 weeks. Efficacy end points included changes in glycemic control, body weight, and β-cell function at baseline, 4 weeks, and 12 weeks. After 12 weeks, mean glycated hemoglobin reductions were 4.03% in the sitagliptin group and 4.13% in the gliclazide group, with a mean difference of -0.097 (95% confidence interval, -0.648 to 0.453), confirming noninferiority. Both groups showed significant FPG reductions at 4 weeks (P < .05). The sitagliptin group achieved faster glycemic targets, greater FPG and body weight reductions, and higher rates of FPG < 6.1 mmol/L (26.2% vs 5.7%; P = .012). No significant differences were observed in β-cell function or hypoglycemia incidence (P > .05). Genetic analysis showed specific single-nucleotide polymorphisms affected drug efficacy: dipeptidyl peptidase-4 rs2909451 TT and rs4664443 GG genotypes showed lower efficacy with sitagliptin, while GLP1R rs3765467 AG and KCNJ11 rs2285676 CC genotypes responded better to sitagliptin. Sitagliptin combined with metformin is noninferior to gliclazide combined with metformin in treatment-naive patients with T2DM with glucotoxicity. Genetic polymorphisms significantly affect drug efficacy, highlighting the importance of personalized medicine. The sitagliptin group achieved glycemic targets more quickly and had greater weight reductions without increased adverse effects.

Genetic variations in IGF2BP2 and CAPN10 and their interaction with environmental factors increase gestational diabetes mellitus risk in Chinese women.

This study aims to investigate the association of the genetic variations in IGF2BP2 and CAPN10 as well as gene-environment interactions with the risk of gestational diabetes (GDM) in Chinese women. A total of 1,566 pregnant Chinese women participated in this case-control study. We employed targeted next-generation sequencing to analyze specific SNPs in IGF2BP2 (rs11927381, rs1470579, rs4402960, rs7640539) and CAPN10/rs2975760. Various genetic models were used to assess the associations of these polymorphisms with GDM risk. Gene-gene and gene-environment interactions were examined using GMDR to identify interaction models, Subsequently, logistic regression was employed to confirm the significance of these models and to evaluate their impact on GDM susceptibility. Our study identified significant associations between the C allele of IGF2BP2/rs11927381 and an increased GDM susceptibility in both dominant (P = 0.031, OR = 1.247) and heterozygote (P = 0.043, OR = 1.239) gene models. Conversely, the heterozygote TC genotype of CAPN10/rs2975760 was associated with a reduced risk of GDM (P = 0.046, OR = 0.766). Increased BMI and O3 levels were linked to a higher GDM susceptibility. We discovered interactions between CAPN10/rs2975760 CC and IGF2BP2/rs11927381 TC genotype that exacerbated GDM risk (P = 0.022, OR = 11.337). Furthermore, interactions between IGF2BP2/rs11927381 and environmental factors were observed, indicating increased GDM risks (BMI: P = 0.004, OR = 1.011; O3: P = 0.013, OR = 1.002; PM2.5: P = 0.042, OR = 1.005；BC: P = 0.048, OR = 1.094; NO3-:P = 0.045, OR = 1.024). GDM is significantly associated with IGF2BP2/rs11927381 and CAPN10/rs2975760 polymorphisms as well as exposure to O3. Furthermore, the interaction between the CAPN10/rs2975760 CC genotype and IGF2BP2/rs11927381 TC genotype, as well as environmental factors (O3, PM2.5, BMI), significantly increases the risk of GDM in Chinese women.