Genotype Frequencies Research Articles

Gene detection of VDR BsmI locus and its approteins, genes and growthplication in rational drug use in patients with osteoporosis.

Aim: This paper determines the polymorphism distribution of the VDR BsmI gene in 350 patients and provides medication recommendations for osteoporosis based on detection results. Materials & methods: Chi-square tests compared genotype and allele frequencies with other populations. Results: Genotype frequencies were 91.66bb, 8.72Bband 0.21% BB, with allelic frequencies of 95.43b and 4.57% B, adhering to Hardy-Weinberg equilibrium. These findings suggest that VDR gene polymorphisms, particularly at the BsmIlocus, play an essential role in bone health and osteoporosis treatment. Genotype-based drug selection reduced adverse reactions from 14 to twocases. Conclusion: These findings improve clinical treatment efficacy and guide rational drug use for osteoporosis patients.

Serum level of interleukin-24 and its polymorphism in eczematic Iraqi patients.

Eczema is a common skin disease associated with inflammation. Interleukin (IL)-24 is crucial in the pathogenesis of inflammatory diseases like eczema. The study objective was the assessment of IL-24 serum levels and its gene polymorphisms in eczematic Iraqi patients. This retrospective case-control study involved 145 participants, divided into 82 patients with eczema and 63 healthy controls. An enzyme-linked immunosorbent assay measured serum IL-24, while polymerase chain reaction and Sanger DNA sequencing were used for genotype analysis. Serum IL-24 level was significantly higher (P value < .001) in patients compared to controls (41.6 [interquartile range (IQR): 28.9-53.6] vs 9.8 [IQR: 0.8-19.6] pg/mL, respectively). DNA sequence illustrated 2 SNPs with polymorphic frequencies (rs1150256 G/A and rs3093425 del/ins). The first SNP (rs1150256 G/A) showed 3 genotypes (GG, AA, and G/A), while the second SNP (rs3093425) showed 3 genotypes (-/G del/Ins, G Ins/Ins, and - del/del). The subsequent investigation revealed the presence of the following findings within the DNA sequence of the PCR amplified region (329bp). In the control group, all participants had GG/G (wild type) genotype/allele for the rs1150256 SNP, while in eczematic patients, 24.4% GG, 50% GA, and 25.6% AA. For the second SNP genotype (rs3093425 del/ins), the genotype frequencies in patients vs control were (24.4% vs 84.1%, 50.0% vs 11.1%, and 25.6% vs 4.8; Del/Del, Del/Ins, and Ins/Ins, respectively). The presence of Ins compared to Del increased the risk of eczema by 8.91 (4.66-17.03); OR (95% CI). In conclusion, IL-24 is a good predictor of eczema and A-allele carrier for rs1150256 SNP, and insertion-allele carrier for rs3093425 SNP is associated with elevated serum IL-24 and higher risk of eczema.

Investigating the Correlation between Genotypes and Hepatic Protein Expression of CYP2C9, CYP2C19, CYP2D6, and CYP3A5 Using Postmortem Tissue from a Danish Population.

The cytochrome P450 (CYP) family of enzymes plays a central role in the metabolism of many drugs. CYP genes are highly polymorphic, which is known to affect protein levels, but for some low frequent CYP genotypes the correlation between genotype and CYP protein expression is less established. In this study, we determined the CYP2C9, CYP2C19, CYP2D6, and CYP3A5 genotypes of 250 Danish individuals included in a postmortem study. For 116 of the individuals, the hepatic CYP protein levels were investigated by a proteomics approach. Overall, we found the postmortem genetic and proteomic data to be in agreement with those of other studies performed on fresh hepatic tissue, showing the usability of postmortem hepatic tissue for this type of investigation. For less investigated genotypes, we could corroborate previously found results: 1) statistically significantly lower levels of hepatic CYP2C9 protein in individuals carrying the CYP2C9*3 variant compared with individuals with two wild type (wt) alleles; 2) comparable levels of CYP2C19 in CYP2C19*2/*17 and CYP2C19*1/*2 individuals; 3) reduced CYP2D6 protein levels in heterozygous individuals with the CYP2D6*3, CYP2D6*4, and CYP2D6*5 gene deletion variants; and 4) significantly lower levels of CYP3A5 protein in CYP3A5*3 homozygous individuals compared with individuals who were heterozygous for the CYP3A5*3 allele or homozygous individuals for the wt alleles. In conclusion, the use of postmortem tissue significantly increases the access to human specimens for research purposes, and postmortem proteomics can be used to investigate the link between CYP genotypes and hepatic protein expression. SIGNIFICANCE STATEMENT: In tissue samples from a large postmortem cohort (n = 250) we determined the CYP2C9, CYP2C19, CYP2D6, and CYP3A5 genotypes. Hepatic CYP protein levels were investigated in 116 individuals using a proteomics approach. For common genotypes, we found results similar to previous knowledge, pointing toward the usability of postmortem tissue. For the less investigated genotypes, we were able to corroborate genotype/protein expression correlations. It is a novel approach to use a large postmortem cohort to investigate genetic/protein expression correlations.

Association of insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme gene (ACE) with Parkinson’s disease and factors risk in eastern Algeria: case–control study

BackgroundThis study aimed to explore the relationship between Parkinson’s disease and insertion/deletion polymorphism (I/D) of the angiotensin-converting enzyme gene (ACE) and to highlight the related risk factors within Eastern Algerian population. A total of 262 individuals were recruited, including 100 PD patients and 162 controls. Polymerase chain reaction technique was employed to determine the ACE polymorphism genotype of each participant. Logistic regression analysis was conducted to examine factors potentially contributing to Parkinson’s disease.ResultsThe mean age of onset of Parkinson’s disease in the patient group was 56.18 ±12.99\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\pm 12.99$$\\end{document}. The results revealed that the D allele of the angiotensin-converting enzyme gene and the DD genotype were most prevalent in both patients and controls. However, there were no significant differences in the genotype and allele frequencies of the I/D polymorphism of the angiotensin-converting enzyme gene between patients and healthy subjects. Cardiovascular disease, diabetes and profession were identified as potential risk factors for Parkinson’s disease.ConclusionThe obtained data indicated no correlation between the angiotensin-converting enzyme I/D gene polymorphism and Parkinson’s disease in our research cohort. Multiple logistic regression analysis revealed that cardiovascular disease, diabetes and profession were possible risk factors for Parkinson’s disease.

Low and High-Normal FMR1 Triplet Cytosine, Guanine Guanine Repeats Affect Ovarian Reserve and Fertility in Women Who Underwent In Vitro Fertilization Treatment? Results from a Cross-Sectional Study.

Dynamic mutations in the 5' untranslated region of FMR1 are associated with infertility. Premutation alleles interfere with prenatal development and increase infertility risks. The number of CGG repeats that causes the highest decrease in ovarian reserves remains unclear. We evaluated the effect of FMR1 CGG repeat lengths on ovarian reserves and in vitro fertilization (IVF) treatment outcomes in 272 women with alleles within the normal range. FMR1 CGG repeat length was investigated via PCR and capillary electrophoresis. Alleles were classified as low-normal, normal, and high-normal. Serum levels of follicle-stimulating hormone and anti-Mullerian hormone (AMH) in the follicular phase of the menstrual cycle were measured, and antral follicles (AFC) were counted. IVF outcomes were collected from medical records. Regarding FMR1 CGG repeat length alleles, 63.2% of women presented at least one low-normal allele. Those carrying low-normal alleles had significantly lower AMH levels than women carrying normal or high-normal alleles. Low-normal/low-normal genotype was the most frequent, followed by low-normal/normal and normal/normal. A comparison of ovarian reserve markers and reproductive outcomes of the three most frequent genotypes revealed that AFC in the low-normal/normal genotype was significantly lower than the low-normal/low-normal genotype. The low number of FMR1 CGG repeats affected AMH levels and AFC but not IVF outcomes per cycle of treatment.

Association of single nucleotide genetic polymorphisms of vitamin D receptor and calcium-sensitive receptor with calcium-containing kidney stones in Chinese Dai populations: a prospective multi-center study.

To evaluate the association between vitamin D receptor (VDRs) and calcium-sensitive receptor (CaSR) gene polymorphisms and calcium-containing kidney stones (CCKS) in Dai populations. A total of 160 CCKS patients and 87 healthy controls were included in this study. CCKS was confirmed using urological computed tomography (CT), plain abdominal radiograph, or surgical lithotomy. Stone samples obtained during surgery were analyzed using infrared spectroscopy. Venous blood and 24-h urine samples were collected and analyzed using Sanger sequencing and high-performance liquid chromatography, respectively. Genetic variants in the VDR gene (rs7975232, rs2228570, rs731236, and rs1544410) and CaSR gene (rs7652589, rs1801725, and rs1042636) were identified through sequence analysis. Analysis of genotype and allele frequencies revealed that the rs7975232 polymorphism in the VDR gene and the rs7652589 allele in the CaSR gene were significantly associated with CCKS. Furthermore, patients carrying the AC and AA genotypes of rs7975232 showed a higher incidence of hypocitraturia compared to those with other genotypes (p < 0.05). The AA and GG genotypes of rs1042636 and the AA genotype of rs7652589 were significantly associated with hypercalciuria (p < 0.05). CCKS in this study population may be closely related to hypocitraturia caused by the VDR locus rs7975232 polymorphism and hypercalciuria caused by the CaSR locus rs1042636 and rs7652589 polymorphism.

Correlation between BMPR1B Gene Polymorphism and some Reproductive Traits in Awassi Sheep

The (BMPR-1B) gene is one of the main genes for ewe fertility. This study was conducted to check the association between BMPR-IB gene polymorphisms and some traits of Awassi. This study was made in Anbar Governorate - (Agricultural Research Department) Al-Dawar. Date of experience collected from 34 ewes at the age of 4-6 years. Next, DNA was extracted and a PCR reaction was performed to amplify blood samples taken from the ewes to confirm the presence of the BMPR1B gene. The sequence was determined using Sanger sequencing technology. The data were then analyzed and compared between sample sequences to determine SNPs, genotype frequencies, allele frequencies, and their association with reproductive and growth traits. The results showed mutations in the heteroplasmy site rs410310346 (T&gt;C) and rs592447725 (G&gt;A). The results indicated that the TC genotype at the mutation site rs410310346 (T&gt;C) was significantly superior (P≤0.05) in ewes whose rates of fertility and body length were higher compared to the CC genotype. The genotypes haven’t got an important effect on the proportion of twins, fertility rate, chest circumference, front height, ewe birth weight, and lamb weight at birth. The relationship of genotype GG and GA at the mutation site rs592447725 (G &gt; A) showed a very significant effect (P≤0.01) on the percentage fertility rate and a noteworthy result (P≤0.05) on body length, height at the front and birth weight of lambs, but there isn’t a big impact. In the percentage of twins, fertility rate, chest circumference, and birth weight of ewes. Therefore, the effect of the BMPR1B gene can be used as a genetic marker to select ewes with good genotypes to improve herd performance.

Influence of matrix metalloproteinase 9 variant rs17576 on ischemic stroke risk and severity in acute coronary syndrome

BackgroundIschemic injury is a common mechanism in both ischemic stroke (IS) and acute coronary syndrome (ACS). Matrix metalloproteinase 9 (MMP-9), an endopeptidase that degrades extracellular matrix, is important in the pathogenesis of IS. The purpose of this study is to evaluate the association between the SNP rs17576 in MMP-9 gene with (1) the risk and severity of acute ischemic stroke in Saudi Arab individuals with recent acute coronary syndrome, and (2) the risk of acute coronary syndrome in Saudi Arab individuals without ischemic stroke. MethodsA case control study of 200 IS patients, 520 ACS patients (without IS), and 500 aged-matched healthy controls were genotyped to detect the MMP-9 polymorphism rs17156. ResultsOur study demonstrated a non-significant difference in the genotype and allele frequencies of the MMP9 rs17576 polymorphism between the patients with IS and patients with ACS without IS (P = 0.31 for the GA genotype, 0.25 for the AA genotype and P = 0.20 for the A allele). AA genotype was found to be statistically significant between IS and control groups; [OR=1.84, 95 % CI (1.08-3.14), p =0.015]. A allele showed a significant difference between the two groups [OR=1.28, 95 % CI (1.00-1.64), p =0.028]. By comparing ACS without IS and controls, AA genotype was significant [OR=1.46, 95 % CI (1.01–2.12), p =0.029]. Stratification by NIHSS score revealed higher mortality and early neurologic deterioration in IS patients with NIHSS score ≥ 16 (p < 0.001, 0.044 respectively). ConclusionWe deduced the lack of association either with allele or genotype frequencies (p>0.05) between the IS cases and the cases of ACS without IS. In contrast there was a significant association of mutant genotype AA between either the IS group or ACS (without IS) group, and the control group. In addition, different rs17576 genotypes were not associated with raised mortality or a tendency to develop early neurologic deterioration.

TaqI polymorphism of VDR gene in colorectal cancer and Crohn’s disease patients

To study the relation of TaqI polymorphism of VDR gene with age, sex and the disease phenotype in patients with colorectal cancer (CRC) and Crohn’s disease (CD) from western regions of Ukraine. Fifty six patients with CRC, 46 patients with CD and 65 control individuals were included in this research. Assessment of TaqI polymorphism was performed using PCR-RFLP method. The genotype-phenotype association for this polymorphism was analyzed. The frequency of tt genotype in patients with CRC is 0.107 and among the control group is 0.138, OR (95% CI 0.248-2.246). The ratio of genotypes TT:Tt:tt in patients with CRC and in control was 37.5%:51.8%:10.7% and 44.6%:41.6%:13.8%. In men with Tt genotype the average age of CRC onset was 57.6 ± 3.6 years, in women with TT genotypethe mean age of the disease onset was 54.5 ± 4.5 years. The frequency of tt genotype in the patients with CD is 0.217 and among the control group is 0.138, OR (95% CI 0.640–4.666). The Tt genotype was detected in a half of patients with CD and TT genotype was found more frequently in control.The ratio of genotypes in men and women with CD was 38.0%:38.0%:24.0% and 20.0%:60.0%:20.0%. Among patients with CD, who underwent surgery, 33.3% individuals were carriers of tt genotype. It was confirmed no statistically significant difference in the allele frequencies and genotype distributions of Taq1 mutation in patients with CRC and CD in comparison to control group. The ratio of men and women with Tt genotype by groups of B1-B3 forms of CD behaviour according to the Montreal classification is differs, in particular, women with Tt genotype are four times more likely to have the B1 form. A study of Taq1 mutation might contribute to the identification of the groups that are at the greatest risk of severe form of CD.

Usefulness of alien sterilizing cytoplasms for the hybrid breeding of triticale (xTriticosecale Wittmack): preliminary results.

To be useful for cereal breeding, cytoplasmic male sterility (CMS) should express the complete sterility of maternal lines and the full restoration of the male fertility of F1 hybrids. The most reliable source of sterilizing cytoplasm for triticale is Triticum timopheevi; however, due to the low frequency of efficient non-restorer genotypes for this cytoplasm, new sources of CMS are needed. In this study, aside from T. timopheevi (T) cytoplasm, three alternative CMS sources were tested: Pampa (P) from Secale cereale L., Aegilops sharonensis (A), and Ae. ventricosa (V). The suitability of these cytoplasms for breeding was assessed based on the male fertility/sterility of F1 hybrids obtained through the manual pollination of CMS maternal lines with 36 triticale cultivars and breeding strains. About half of the hybrids with each type of cytoplasm were fully fertile and produced more than 30 grains per bagged spike. The highest percentage was found in hybrids with P cytoplasm (58.33%) and the lowest in hybrids with A cytoplasm (44.44%). Male sterility was observed in hybrids with P cytoplasm (16.67%) and A cytoplasm (16.67%) but not in hybrids with T or V cytoplasm. In terms of practical aspects, male sterility systems with P or A cytoplasm exhibit similarity in their ability to restore male fertility that differ from the T and V cytoplasms. Although all studied cytoplasms exhibited some disadvantages for breeding purposes, none should be definitively classified as unacceptable for future breeding programs regarding the development of triticale hybrid cultivars.

Association between matrix metalloproteinase-9-1562C/T gene polymorphism and MMP-9 serum level in rheumatoid arthritis

ABSTRACT Background Rheumatoid arthritis (RA) is an autoimmune disease indicated by joint inflammation and cartilage destruction. Matrix metalloproteinase (MMP) enzymes play an influential role in inflammation by affecting the invasion and degradation of anatomical barriers. In this way, the current study investigated the relationship between the MMP-9-1562C/T gene polymorphism and this enzyme’s serum level in RA. Methods The serum levels of MMP-9 in RA patients and healthy controls were measured using the enzyme-linked immunosorbent assay (ELISA). RA was confirmed using rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), and C-reactive protein (CRP). Then the MMP-9-1562C/T gene polymorphism was analyzed utilizing polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Also, multivariate analysis investigated the connection between this polymorphism and the risk of RA. Results In this study, the increase of MMP-9 in patients due to the development of single nucleotide polymorphism in the promoter region of this gene (−1562 C→T) was confirmed by increasing the frequency of heterozygous genotype (CT). Logistic regression analysis also demonstrated that the chance of development of RA is higher in people with CT/CC genotype than in other alleles. Conclusions We demonstrated that MMP-9-1562C/T gene polymorphism can play a significant role in the occurrence of RA.

Analysis of single nucleotide polymorphisms of the metabotropic glutamate receptors in a transgender population.

Gender incongruence (GI) is characterized by a marked incongruence between an individual's experienced/expressed gender and the assigned sex at birth. It includes strong displeasure about his or her sexual anatomy and secondary sex characteristics. In some people, this condition produces a strong distress with anxiety and depression named gender dysphoria (GD). This condition appears to be associated with genetic, epigenetics, hormonal as well as social factors. Given that L-glutamate is the major excitatory neurotransmitter in the central nervous system, also associated with male sexual behavior as well as depression, we aimed to determine whether metabotropic glutamate receptors are involved in GD. We analyzed 74 single nucleotide polymorphisms located at the metabotropic glutamate receptors (mGluR1, mGluR3, mGluR4, mGluR5, mGluR7 and mGluR8) in 94 transgender versus 94 cisgender people. The allele and genotype frequencies were analyzed by c2 test contrasting male and female cisgender and transgender populations. The strength of the associations was measured by binary logistic regression, estimating the odds ratio (OR) for each genotype. Measurement of linkage disequilibrium, and subsequent measurement of haplotype frequencies were also performed considering three levels of significance: P ≤ 0.05, P ≤ 0.005 and P ≤ 0.0005. Furthermore, false positives were controlled with the Bonferroni correction (P ≤ 0.05/74 = 0.00067). After analysis of allele and genotypic frequencies, we found twenty-five polymorphisms with significant differences at level P ≤ 0.05, five at P ≤ 0.005 and two at P ≤ 0.0005. Furthermore, the only two polymorphisms (rs9838094 and rs1818033) that passed the Bonferroni correction were both related to the metabotropic glutamate receptor 7 (mGluR7) and showed significant differences for multiple patterns of inheritance. Moreover, the haplotype T/G [OR=0.34 (0.19-0.62); P<0.0004] had a lower representation in the transgender population than in the cisgender population, with no evidence of sex cross-interaction. We provide genetic evidence that the mGluR7, and therefore glutamatergic neurotransmission, may be involved in GI and GD.

CFTR mutations and phenotypic correlations in people with cystic fibrosis: a retrospective study from a single centre in south India

Emerging data reveal higher-than-expected prevalence of cystic fibrosis (CF) among non-European populations worldwide including in the Indian subcontinent. Systematic analyses of the CFTR mutation profile, and genotype-phenotype correlations among people with CF from south, east, or northeast India have not been reported before. We wanted to identify CFTR mutations in people with CF, and highlight novel variants, selective phenotypic correlations, and regional variances within India. A retrospective study was conducted at Christian Medical College, Vellore, India (single tertiary referral hospital) from September 2010 to August 2022, involving 120 people with CF from (i) four south Indian states (Tamil Nadu, Andhra Pradesh, Kerala, Karnataka), (ii) in and nearby regions of West Bengal, India and (iii) Bangladesh. Comprehensive CFTR mutation analyses were done by Next-Generation Sequencing, and variants were categorized per American College of Medical Genetics guidelines and compared with validated Locus-specific databases. Demographic characteristics, mutation profile, novel mutations, selective phenotype correlations, and regional variances were assessed. In 120 people with CF, 55 CFTR variants were identified, including six novel variants. F508del was the predominant mutation, yet with a lower allele frequency than reported among European populations (27% versus 70%). Phenotypic correlations suggested high mutational pathogenicity causing severe multi-organ morbidity, and death in 27%. Milder variants associated with pancreatic sufficiency were also evident in 23% of people with CF. Statistically significant regional variances were noted in genotype frequency, and clinical phenotype among people with CF from the two regions. Hotspot exons and introns that could potentially help create targeted mutation panels were identified. The identification of 55 different CFTR variants among 120 people with CF describes the diversity of mutations noted in India, while also revealing the challenges that providers may encounter in timely diagnosis and treatment of CF. However, these single-centre data have specific limitations and cannot be generalised to all people with CF from India or to those of non-European origin. Our data on regional CFTR mutations contribute to the emerging national registry on CF epidemiology in India, help formulate diagnostic and newborn screening algorithms, help optimise clinical care, and highlight urgency to improve access to life-changing modulator therapy. Cystic Fibrosis Foundation, USA (towards the CF-India Demonstration Project) and Christian Medical College, Vellore, India.

High Frequency of Ancestral Haplotype A of Fatty Acid Desaturase Genes in the Yakut Population.

Aims: The purpose of this study was to study the correlation of the body weight of Yakuts with the variability of polymorphisms rs174537, rs174546 and rs3834458 of the FADS1 - FADS2 region to identify the connection of certain genotypes with obesity. Materials and Methods: For genotyping, classical methods of PCR-RFLP analysis were used. A sample of 446 DNA samples from Yakut volunteers without chronic diseases (143 women and 303 men) was studied. Results: The predominance of the ancestral alleles of SNPs rs174537, rs174546 and rs3834458 was established in all of our studied groups. Analysis of the odds ratio of allele and genotype frequencies in patients with normal BMI, high BMI and obesity did not show statistically significant values. We did not find an association between rs174537, rs174546 and rs3834458 with obesity, but we did not take into account the diet of the subjects, which may have had a stronger effect on BMI. Analysis of pairwise linkage disequilibrium and assessment of haplotypes for 3 SNPs in the FADS1 and FADS2 genes showed strong linkage of all three SNPs to each other (r2 = 0.93-0.96). Conclusions: According to the result of genotyping of SNP rs174537, the frequency of haplotype A in the Yakut population was 0.76 and, in comparison with other world data, is quite high. Which in turn is associated with lower conversion of short-chain polyunsaturated fatty acid to long-chain polyunsaturated fatty acid. Accordingly, a shift in nutrition towards more plant foods can negatively impact the health of the Yakuts. At the moment, the exact dosage of polyunsaturated fatty acids (PUFAs) for humans has not yet been established, but judging by the fact that all recommendations are mainly made on the basis of European populations, in connection with the results of the study, the Yakuts have a particularly high need for PUFAs.

Apolipoprotein E Gene Variation in Pakistani Subjects with Type 2 Diabetes with and without Cardiovascular Complications.

Background: Apolipoprotein E (APOE) gene polymorphism has been implicated in the pathogenesis of various metabolic disorders, including type 2 diabetes mellitus (T2DM). Type 2 diabetes mellitus (T2DM) is a major public health concern worldwide, including in Pakistan. Cardiovascular problems linked with T2DM have a significant impact on individuals and society. The goal of this study is to investigate the relationship between Apolipoprotein E (ApoE) genotypes, dyslipidemia, and cardiovascular complications such as ischemic heart disease (IHD) and stroke. Methods: This study was carried out on 260 subjects divided into controls and diabetics. The diabetics were further divided into four subgroups such as D1: diabetics without cardiovascular issues, D2: diabetics with heart disease, D3: diabetics with stroke, and D4: diabetics with both heart disease and stroke. Anthropometric parameters (age, BMI) and risk factors (smoking, diabetes duration, hypertension) were assessed in all groups. Serum levels of TC, TG, LDL, HDL, VLDL, creatinine, BSF, and HbA1c were also measured. Apolipoprotein E gene polymorphism was determined using PCR-RFLP. Results: Hypertension, BMI, and dyslipidemia are defined as elevated levels of total cholesterol, triglycerides, LDL, and VLDL, and decreased levels of HDL. Uncontrolled hyperglycemia (elevated fasting blood sugar and glycated hemoglobin) in T2DM was linked to vascular complications such as IHD and stroke. Hypertension was prevalent in 79.3% of the population. Stage 2 hypertension was more prevalent in all age groups. It was also noted that common genotypes in the Pakistani population are 3/3, 4/4, 2/3, and 3/4. The frequency of genotypes 3/4 and 2/3 is highest in diabetics with stroke. Genotype 3/3 is present frequently in diabetics with IHD/stroke and patients with both these complications. However, genotype 4/4 is most frequently found in diabetics with IHD. Conclusions: It is concluded that BMI, hypertension, hyperglycemia, atherosclerosis, and dyslipidemia are linked with cardiovascular complications of type 2 diabetes. Apolipoprotein E gene polymorphism is associated with cardiovascular disease in patients with diabetes by affecting the lipid profile.

Cytomegalovirus Antiviral Resistance Among Kidney Transplant Recipients in a Phase 3 Trial of Letermovir vs Valganciclovir Prophylaxis

Abstract Background In a phase 3 trial, letermovir was noninferior to valganciclovir for cytomegalovirus (CMV) disease prophylaxis in kidney transplant recipients who were CMV-seronegative and received kidneys from donors who were CMV-seropositive. Genotypic antiviral resistance and CMV glycoprotein B (gB) genotype are reported. Methods Plasma samples with detectable CMV DNA were sequenced for the presence of known letermovir and valganciclovir resistance-associated amino acid substitutions (RASs) encoded by CMV gene regions (UL51, UL54, UL56, UL89, UL97) and prevalence of gB (UL55) genotypes (gB1–gB5). Results Among participants, 84 of 292 (letermovir) and 93 of 297 (valganciclovir) had evaluable data for ≥1 gene target. Letermovir RASs were not detected in participants who received letermovir prophylaxis; however, 3 had valganciclovir RASs (pUL97). Twelve participants who received valganciclovir prophylaxis had valganciclovir RASs (pUL54, pUL97), and 1 who did not receive letermovir during the trial had letermovir RASs (pUL56). All but 1 participant responded to valganciclovir treatment irrespective of breakthrough CMV DNAemia or frequency of RASs. gB1 was the most frequent genotype across all participants and subgroups. Conclusions Letermovir RASs were not detected with letermovir prophylaxis, supporting a low risk for development of resistance in kidney transplant recipients who were CMV-seronegative and received kidneys from donors who were CMV-seropositive. Clinical Trials Registration ClinicalTrials.gov, NCT03443869; EudraCT, 2017-001055-30.

A Study on the Association Between Siglec-1 Gene Polymorphism and Susceptibility in Patients with Chronic Obstructive Pulmonary Disease in Luohe Area

Objective: To analyze the association between Siglec-1 gene polymorphism and susceptibility to chronic obstructive pulmonary disease (COPD) in the population of the Luohe area. Methods: A case-control study (150 COPD patients and 150 healthy controls) was conducted to analyze the Siglec-1 allele in two groups of individuals using single nucleotide polymorphism (SNP) high-throughput detection technology, and the frequencies of each allele were compared. Results: The frequency of rs611847 heterozygous A/G genotype in COPD patients was significantly lower in females than in healthy controls (OR = 0.282, 95% CI = 0.085–0.938, P = 0.039); among smokers, the frequency of rs3859664 and rs6084444 genotypes in COPD patients was significantly higher than that in the healthy control group (OR = 2.028, 95% CI = 1.111–3.704, P = 0.021; OR = 1.836, 95% CI = 1.033–3.262, P = 0.038). Conclusion: Among the COPD population in the Luohe area, there is a significant correlation between the genotypes of three SNPs loci, rs3859664, rs6084444, and rs611847 and susceptibility to COPD in different subgroups of the population. The rs3859664 A/G-A/A and rs6084444 A/G-G/G genotypes can increase the risk of COPD in smokers; the rs611847 heterozygous A/G genotype can reduce the risk of COPD in both female and smoking populations.

Polymorphism of apoptosis marker genes in the blood of indigenous people with gastric cancer in the Republic of Tyva

Introduction. Russia is among the leaders in incidence and mortality from gastric cancer (GC). The incidence of gastric cancer in the Republic of Tyva is especially abnormally high. Currently, there is interest in studying genetic factors in various types of cancer. But for GC, such research is not enough.Aim. To study the polymorphism of the apoptosis marker genes CASP9 (rs1052576), TP53 (rs1042522), FAS/APO-1 (rs2234767) in the blood of indigenous people with GC in the Republic of Tyva.Materials and methods. 107 Tuvinians were examined (47 people with GC and 60 persons in the control group). The diagnosis of GC was established on the basis of a comprehensive laboratory, instrumental and morphological examination by oncologists at the Republican Oncology Dispensary. Genotyping of polymorphisms rs1052576 CASP9, rs2234767 FAS/APO-1 and rs1042522 TP53 was carried out in all 47 patients with GC and in 60 people in the control group using the polymerase chain reaction method from DNA samples isolated from venous blood.Results. In patients with GC, compared with healthy individuals, the mutant allele G (44.7% versus 27.5%; p = 0.01) and the homozygous genotype GG (23.4% versus 6.7%; p = 0.03) of polymorphism rs1042522 TP53, as well as mutant allele A (57.4% versus 32.5%; p &lt; 0.001) and homozygous genotype AA (31.9% versus 15.0%; p = 0.05) of polymorphism rs2234767 FAS/ APO-1 were more often registered among indigenous inhabitants of the Republic of Tyva. The frequency of various genotypes and alleles of the polymorphism rs1052576 CASP9 did not differ significantly between patients with GC and healthy individuals.Conclusion. Based on these results, it can be assumed that the A allele of rs2234767 FAS/APO-1 and the disruption of the anti-oncogenic function of the p53 protein produced by the G allele of rs1042522 TP53 are associated with GC and can be used as markers to determine increased risk in the population of indigenous residents of the Republic of Tyva.

IL10 promoter variants are associated with gene expression but they are not markers of susceptibility to acute coronary syndrome

Interleukin-10 (IL-10) is an immunomodulatory cytokine that plays a pivotal role in the pathogenesis of acute coronary syndromes (ACS). Here, we evaluated the role of IL10 promoter variants as markers for ACS susceptibility in Western Mexican patients as well as its association with IL10 mRNA and IL-10 plasma levels. Three promoter variants (− 1082 A > G, − 819 T > C and − 592 A > C) were analyzed in 300 ACS patients and 300 control group (CG) individuals. IL10 relative gene expression was evaluated in peripheral blood mononuclear cells (PBMC) and IL-10 levels were quantified in plasma. The allelic, genotypic and haplotypic frequencies did not show significant differences between groups. ACS patients had sevenfold higher mRNA IL10 level compared to CG (p = 0.0013). Homozygous C/C carriers in both − 819 T > C and − 592 A > C variants had 0.4-fold higher IL10 mRNA expression than heterozygous and polymorphic allele homozygous genotypes (p = 0.0357) in ACS group. There were significant differences in plasma IL-10 levels in CG and ACS group (1.001 vs 1.777 pg/mL, p = 0.0051). The variants were not markers of susceptibility to ACS in Western Mexican individuals. ACS patients showed higher IL10 expression than CG individuals which could be mediated by − 819 T > C and − 592 A > C variants and pharmacotherapy.

The Effect of Genetic Variants of SLC22A2 (rs662301 and rs315978) on the response to Metformin in type 2 Saudi diabetic patients

PurposeTo investigate the allelic and genotypic frequencies of the two genetic variations, NC_000006.12: g.160275887C > T (rs662301) and NC_000006.12:g.160231826 T > C (rs315978), in the SLC22A2 gene among the Saudi population. The primary goal is to elucidate potential associations with these genetic variations and the response to metformin therapy over 6 months to enhance our knowledge of the genetic basis of Type 2 Diabetes Mellitus (T2DM) and its clinical management in the Saudi population. Materials/Methods76 newly diagnosed T2DM patients, aged 30 to 60, of both sexes and Saudi origin, were treated with metformin monotherapy. Blood samples were collected before and after 6 months of therapy,80 healthy individuals were included as controls. Genomic DNA was extracted. Genotyping of the SLC22A2 genetic variations was performed using TaqMan® SNP Genotyping Assays. Binary logistic regression was utilized to evaluate how certain clinical parameters influence T2DM concerning the presence of SLC22A2 gene variants. ResultsAmong these patients, 73.3 % were responders, and 26.7 % were non-responders. For these variants, no statistically significant differences in genotype or allele frequencies were observed between responders and non-responders (p = 0.375 and p = 0.384 for rs662301; p = 0.473 and p = 0.481 for rs315978, respectively). For the SLC22A2 variant rs662301, the C/C genotype was significantly associated with increased T2DM risk with age and elevated HbA1c levels. Similarly, rs315978 revealed higher T2DM susceptibility and HbA1c elevation in C/C genotype carriers, specifically with advancing age compared to individuals with C/T and T/T genotypes. ConclusionThe study offers insights into the genetic landscape of T2DM in Saudi Arabia. Despite the absence of significant associations with treatment response, the study suggests potential age-specific associations, this highlights the complexity of the disease. This research underscores the necessity for expanded research, considering diverse populations and genetic factors, to develop personalized treatment approaches. This study serves as a foundation for future investigations into the Saudi population, recognizing the need for a larger sample size.