Preliminary investigation of MMP8 (rs11225395) and MMP9 (rs3787268) polymorphisms association with breast cancer risk in pashtun women of Pakistan.

BACKGROUND: Single Nucleotide polymorphisms (SNPs) in MMP8 and MMP9 have been widely associated with breast cancer risk in different ethnicities with inconsistent results. There is no such study conducted so far in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. Therefore, this study was conducted to check MMP8 (rs11225395) and MMP9 (rs3787268) polymorphism with breast cancer risk in the selected population. METHODS: This study, consisting of 300 breast cancer patients and 168 gender and age-matched healthy controls was subjected to confirm MMP8 and MMP9 polymorphisms. Clinicopathological data and blood samples were taken from all the participants. DNA was extracted and SNPs were confirmed using the T-ARMS-PCR protocol. RESULTS: Based on our study results, significant associations were observed between the MMP8 rs11225395 risk allele (G) and increased breast cancer risk, with the G allele frequency higher in patients (65%) compared to controls (51%) (OR = 1.752, 95% CI = 1.423-3.662, p = 0.002). Genotypes GG (OR = 4.218, p = 0.005) and AG (OR = 7.286, p = 0.0001) of MMP8 rs11225395 were also significantly associated with elevated breast cancer risk. Similarly, MMP9 rs3787268 exhibited a higher frequency of the risk allele (A) in breast cancer cases (81%) compared to controls (41%), correlating strongly with increased risk (OR = 6.320, p = 0.0001). Genotypes AA (OR = 14.500, p = 0.0001) and AG (OR = 2.429, p = 0.077) of MMP9 rs3787268 containing the risk allele showed significant associations with heightened breast cancer risk. Subgroup analyses based on age, disease progression, tumor size, and grade revealed noteworthy associations for both MMP8 rs11225395 and MMP9 rs3787268. MMP8 rs11225395 genotypes displayed significant correlations with age (p = 0.066), disease progression (p = 0.0001), larger tumor size (p = 0.005), and higher tumor grade (p = 0.006). Similarly, MMP9 rs3787268 genotypes were significantly associated with age (p = 0.001), disease progression (p = 0.010), larger tumor size (p = 0.018), and higher tumor grade (p = 0.037). Logistic regression analyses further underscored these genetic variants' potential role as biomarkers in breast cancer, particularly in relation to specific hormone receptor statuses such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) positivity. CONCLUSION: The results revealed significant associations between the mutant alleles and genotypes of MMP8 (rs11225395) and MMP9 (rs3787268) with increased breast cancer risk in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. However, more investigation will be required on large data sets to confirm the selected SNPs and other SNPs in the selected and other related genes with the risk of breast cancer.

Study of adiponectin gene (rs1501299) polymorphism and serum adiponectin level in patients with primary knee osteoarthritis.

BACKGROUND: We aimed to study, for the first time in the Egyptian population, the relationship between the serum adiponectin level in knee osteoarthritis (KOA) patients and its correlation with clinical, radiological, and ultrasonographic characteristics. Additionally, investigate the relationship between the adiponectin (ADIPOQ) gene rs1501299 (+ 276G/T) polymorphism and KOA susceptibility and severity. METHODS: This case-control study enrolled 40 patients with primary KOA and 40 matched controls. All patients underwent physical examination of the knee, pain assessment using the visual analogue scale (VAS), and functional evaluation by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Severity of KOA was assessed by Kellgren Lawrence (KL) grading scale and ultrasonography grading systems. Serum adiponectin levels and adiponectin (ADIPOQ) gene single nucleotide polymorphism (SNP) (rs1501299) genotyping were done for all patients and controls. RESULTS: The study included 40 patients with primary symptomatic KOA and 40 controls with comparable age, sex, and body mass index. The genotype of the rs1501299 (+ 276G/T) polymorphism of the ADIPOQ gene was determined using TaqMan allelic discrimination. An enzyme-linked immunosorbent test was used to measure the level of serum adiponectin. The Western Ontario and McMaster Universities Osteoarthritis (WOMAC) score was used to assess functional capability, while the visual analogue scale was utilised to assess knee pain. Using the Kellgren-Lawrence (KL) grading method and global femoral cartilage (GFC) ultrasound grading, the severity of KOA was assessed. No significant differences between patients and controls as regards the genotype distributions and allele frequencies (p = 0.400, p = 0.507, respectively) of ADIPOQ gene rs1501299 (+ 276G/T) polymorphism. Furthermore, serum adiponectin level was significantly higher in the patients compared to healthy subjects (p < 0.001). Additionally, adiponectin level had a significant negative correlation with disease severity as evaluated by KL and GFC grading (r=-0.351, p = 0.027 and r=-0.397, p = 0.011, respectively). CONCLUSIONS: The ADIPOQ gene rs1501299 (+ 276G/T) polymorphism was not associated with KOA severity or vulnerability. The level of adiponectin considerably reduced as the severity of KOA rose, indicating that adiponectin may have a preventive effect in KOA.

Decoding the genetic influence of CT60 non-coding polymorphism in CTLA-4 gene and sCTLA-4 biomarker with rheumatoid arthritis in the Indian population.

BACKGROUND: Cytoplasmic T Lymphocyte Antigen - 4 (CTLA-4) gene encodes an immunoregulatory receptor expressed on surface of activated T-cells to mediate peripheral tolerance against self-antigen. It suppresses auto-reactive T-cell proliferation either by inactivation or apoptosis of T-cells. The CTLA-4 mRNA undergoes alternative splicing to synthesize a native soluble form of CTLA-4 (sCTLA-4) protein, which lacks exon 3 that encodes for transmembrane region. As a result, sCTLA-4 circulates as a soluble serum protein and acts as an immunoregulator molecule to maintain homeostasis in the blood. MATERIALS AND RESULTS: Techniques coupled with quantitative Polymerase Chain Reaction (qPCR) and High-Resolution Melting Analysis (HRMA) were used to screen CTLA-4 3'Untranslated Region (UTR) CT60 (A/G) rs3087243 Single Nucleotide Polymorphism (SNP) and their association with Rheumatoid Arthritis (RA) in the Indian population. In addition, we also evaluated the concentration of sCTLA-4 serum protein in RA patients carrying rs3087243 SNP with different genotypes (A/A, G/A, and G/G). Statistical analysis of Odds Ratio (OR), Confidence Interval (C.I), and Relative Risk (RR) have shown that frequency of CTLA-4 rs3087243 SNP G/G genotype was significantly associated with RA in the Indian population (OR 1.7140; CI = 1.0765 to 2.7290; RR = 1.5434; p = 0.0232). The sCTLA-4 concentration was also significantly lower in RA patients carrying rs3087243 SNP G/G genotype than control group (p < 0.001). CONCLUSION: Co-inheritance of CTLA-4 signal peptide and 3'UTR SNPs may activate RAPP pathway. Downregulation of CTLA-4 and sCTLA-4 serum protein by rs3087243 SNP can increase the hyperactivation of T-cells, which causes RA.

Molecular investigation of MEFV gene polymorphisms among patients with familial mediterranean fever-like symptoms.

The diagnosis of familial Mediterranean fever (FMF) is primarily based on clinical standards. The purpose of this study was to investigate the relevance of Mediterranean fever (MEFV) genetic testing in the diagnosis of FMF as well as to identify the most frequent variant alleles and their relationship to clinical symptoms in Egyptian patients. Egyptian patients with a clinical suspicion of having FMF were studied in order to determine MEFV genotypes. Each patient was meticulously evaluated through an extensive collection of their medical history, a thorough clinical examination, and a series of laboratory tests, encompassing CBC, ESR, and CRP measurements. The MEFV variant screening procedure included the use of reverse dot blot hybridization. The average age of our patients when they were given a diagnosis was 22.8 ± 1.404 years old. The predominant clinical manifestations identified were abdominal pain, fever, and arthralgia.  Molecular interrogation of the MEFV gene unveiled that a significant proportion of the cohort, constituting 72 individuals (60%), displayed heterozygosity, whereas a smaller fraction, comprising 12 subjects (10%), demonstrated homozygosity and an equivalent number (10%) exhibited compound heterozygosity. Pertaining to the distribution of allele variants, E148Q emerged as the most prevalent, succeeded by M694I, accounting for 12.5% of the cases, and M680I (G/A), representing 10.41%. This notable prevalence of heterozygous genotypes among the Egyptian demographic, preliminarily identified as potential FMF cases, underscores the imperative for molecular diagnostics to enhance the precision of FMF identification.

Association Study of 3-untranslated region Haplotype of Human leukocyte antigen-G Gene with Lupus.

Background: Human leukocyte antigen-G (HLA-G) is a pivotal protein involved in immune regulation and tolerance, while systemic lupus erythematosus (SLE) is a multifaceted autoimmune condition influenced by genetic and environmental factors. Research indicates that variations and mutations in HLA-G may impact SLE development. Objective: This study aimed to explore the relationship between polymorphisms in the 3'-untranslated region (UTR) of the HLA-G gene and SLE. Methods: DNA from 100 SLE patients and 100 controls was analyzed using polymerase chain reaction to amplify the target sequence. Allele and genotype frequencies were determined, and haplotypes were assessed using Haploview v.4.2 software, with linkage disequilibrium calculated. Results: Findings revealed that the +2960 Ins allele was significantly linked to SLE as a risk factor, with the Del allele showing a protective effect. In addition, the +3010C allele and +3187A allele were significantly associated with SLE at both allele and genotype levels. The +3142 GG homozygote was notably linked to SLE at the genotype level. Haplotype analysis identified UTR-2 haplotypes as risk factors for SLE, whereas the UTR-1 haplotype was protective, shedding light on genetic factors influencing SLE risk. Conclusion: This study underscores the importance of HLA-G gene 3'-UTR polymorphisms in SLE susceptibility, suggesting their potential as diagnostic or therapeutic targets.

Association of MTR and MTRR polymorphisms with recurrent pregnancy loss: a case control study.

BACKGROUND: In light of several epidemiological studies, the etiology of recurrent pregnancy loss is complex. One of the most frequent causes of women experiencing inexplicable recurrent pregnancy loss is maternal thrombophilia. Hence, the association between genetic polymorphisms causing thrombophilia and recurrent pregnancy loss needs to be explored. AIM: Is to study the relation of polymorphisms affecting folate pathway mainly, 5-Methytetrahydrofolate-Homocysteine Methyltransferase (MTR A2756G) and 5-Methytetrahydrofolate-Homocysteine MethyltransferaseReductase (MTRR A66G) with recurrent pregnancy loss. METHODS: It is a case-control study. Four hundred participants were enrolled. Two hundred participants with unexplained recurrent pregnancy loss (case group) and two hundred healthy fertile participants (control group). All participants were screened for (MTR A2756G) and (MTRR A66G). DNA was extracted using salting out method followed by genotyping via Real-time PCR. RESULTS: Mutant homozygous genotype (GG) in MTRR A66G was statistically significantly among RPL group in comparison to controls. (GG vs. AA) had odds ratio and confidence interval of 1.22(1.12-2.23), P = 0.012. (GG) increased the liability 1.2 folds for recurrent pregnancy loss. Mutant homozygous genotype (GG) in MTR A2756G was not correlated with the risk of recurrent pregnancy loss. (GG vs.AA) = (1.13(0.56-2.29)), P = 0.7 CONCLUSION: MTRR A66G increases susceptibly for recurrent pregnancy loss among Egyptian women.

Genotype Analysis of the JR Blood Group in an East Asian Population Using Tetra-Primer ARMS-PCR.

OBJECTIVE: The JR blood group system, officially designated ISBT JR 032, consists of a single antigen called Jra. This is a high frequency antigen in most populations. The Jr(a-) phenotype is more prevalent in Japanese and Asian populations. Individuals with the Jr(a-) blood type can be recognized incidentally by the production of anti-Jr(a) antibodies and verified by the existence of two null ABCG2 alleles. METHODS: We used direct sequencing to analyze the genotype frequency of the ABCG2 null allele (c.376C>T, rs72552713) and compared it with East Asian genomic databases. We developed tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR), which is a simple, precise method for determining an individual's genotype and suitable for clinical use, and analyzed a cohort of 300 healthy Koreans. RESULTS: Using direct sequencing, we found that 14 individuals in the cohort carried a heterozygous ABCG2 null allele. We optimized the ARMS-PCR technique to detect and identify this null allele precisely. We identified the presence of this null allele in a heterozygous state using ARMS-PCR. CONCLUSION: The minor allele frequency of the ABCG2 null allele in the Korean cohort was 2.3%. The estimated genotype frequencies of homozygotes and heterozygotes for this null allele are 0.05% and 4.56%, respectively. The newly developed ARMS-PCR assay would be useful for determining the Jr(a-) antigen status in patients who produce anti-Jr(a) antibodies as well as for selecting Jr(a-) blood donors.

Frequency of pharmacogenomic variants affecting safety and efficacy of immunomodulators and biologics in a South Asian population from Sri Lanka.

BACKGROUND: Immunomodulators are important for management of autoimmune diseases and hematological malignancies. Significant inter-individual variation in drug response/reactions exists due to genetic polymorphisms. We describe frequency of identified genetic polymorphisms among Sri Lankans. METHODS: Sri Lankan data were obtained from an anonymized database of 670 participants. Data on variants and global distribution of Minor Allele frequency (MAF) of other populations (South Asian, Ashkenazi-Jewish, East-Asian, European-Finnish, European-non-Finnish, Latino-American, African/African-American) were obtained from pharmGKB online database. RESULTS: SLC19A1 (rs1051266) variant had a MAF (95% CI) of 63.3% (60.7-65.9). Other common variants included FCGR3A (rs396991), MTHFR (rs1801133), ITPA (rs1127354), CYP2C9*3 (rs1057910) and NUD15*3 (rs116855232), with MAFs of 35.3% (32.7-37.9), 12.2% (10.4-13.9), 10.9% (9.2-12.6), 9.8% (8.2-11.4), 8.3% (6.8-9.8) respectively. Less commonly present variants included CYP2C9*2 (rs1799853) (2.5%[1.7-3.4]), TPMT*3C (rs1142345) (1.9%[1.1-2.6]), TPMT*3B (rs1800460) (0.2%[0-0.5]), CYP3A5*6 (rs10264272) (0.2%[0-0.4]) and CYP3A4*18 (rs28371759) (0.1%[0-0.2]). The SLC19A1 (rs1051266), NUD15*3 (rs116855232), CYP2C9*3 (rs1057910), FCGR3A (rs396991), and ITPA (rs1127354) showed significantly higher frequencies in Sri Lankans compared to many other populations, exceptions include FCGR3A in Ashkenazi-Jewish and ITPA in East-Asians. Conversely, MTHFR (rs1801133), TPMT*3B (rs1800460), and CYP2C9*2 (rs1799853) were significantly less prevalent among Sri Lankans than in  many other populations. Sri Lankans exhibited lower prevalence of TPMT*3C (rs1142345) compared to European-non-Finnish, Latino-Americans, and African/African-Americans; CYP3A4*18 (rs28371759) compared to East-Asians; and CYP3A5*6 (rs10264272) compared to African/African-Americans and Latino-Americans. CONCLUSION: Sri Lankans exhibit higher frequencies in variants reducing methotrexate efficacy (SLC19A1), increasing azathioprine myelotoxicity (NUDT15), and lower frequencies in variants linked to increased azathioprine toxicity (TPMT*3B, TPMT*3C), reduced tacrolimus efficacy (CYP3A4*18), and methotrexate toxicity risk (MTHFR). Beneficial variants enhancing rituximab efficacy (FCGR3A) are more prevalent, while those reducing tacrolimus dosage (CYP3A5*6) are less common. This highlights need for targeted medication strategies to improve treatment outcomes.

Relationship between rs1410996 polymorphism of CFH gene and essential hypertension patients of Han from Yunnan Province.

OBJECTIVE: To explore the relationship between rs1410996 polymorphism of CFH gene and essential hypertension (EH) in the Yunnan Han population. METHODS: rs1410996 of CFH gene was genotyped based on the collected clinical phenotypes of the EH patients (n = 520) and healthy people (n = 494). RESULTS: On the genotype model and dominance model, there was no relationship between rs1410996 of CFH gene and EH after adjustment (P > 0.05). On the dominance model of male EH patients, the pulse pressure (PP) level of CC genotype carriers was higher than that of (CT + TT) genotype carriers after adjustment (P < 0.05). CONCLUSION: rs1410996 of CFH gene has no correlation with the genetic susceptibility to EH in the Yunnan Han population, but it is related to the PP level in male patients.

Rhesus Macaques: VNTR Polymorphism of the FCGRT Gene.

Variable number tandem repeat (VNTR) polymorphisms of the human neonatal IgG Fc receptor α-chain gene (FCGRT) are known to influence the expression levels of FCGRT and IgG in serum. Monkeys are considered to be a relevant biological model for studying the effects of immunobiological drugs. The study determined the functional VNTR polymorphisms of the FCGRT gene in 109 male rhesus macaques from the nursery of the Kurchatov Complex of Medical Primatology. PCR amplification of samples was carried out followed by electrophoretic separation of DNA fragments in a 2% agarose gel. Individual DNA amplification products were sequenced (according to Sanger system) in forward and reverse directions to confirm the specificity. The genotyping showed that the VNTR polymorphism of the FCGRT gene in the studied population of rhesus macaques is presented by 9 variants. The frequency of the VNTR5 allele associated with lower IgG levels was 14.2%, and the most common one was the VNTR7 allele (25.2%). We also identified alleles that have not been previously reported: VNTR3, VNTR4, VNTR6, VNTR8, and VNTR9. The study allows to consider rhesus macaques as a potential model for studying the immunological response depending on the genetic VNTR variant of FCGRT.

Unveiling population structure and selection signatures of riverine and genetically improved rohu, Labeo rohita using genome wide SNPs.

BACKGROUND: Captive breeding, along with artificial selection can significantly impact population structure by influencing allele frequencies and driving populations towards specific adaptation. Selective sweeps are powerful forces in shaping genetic variation within populations and can drive rapid spread of beneficial alleles while simultaneously reducing genetic diversity in localized regions of the genome. The present work was undertaken to assess the genetic structure and consequences of artificial selection in 10th generation of genetically improved rohu by comparing with wild populations. METHODS AND RESULTS: The present study used 11,022 high-quality genome wide SNPs to compare the population genetic structure and signatures of selection between Jayanti rohu population and its wild counterpart. Outlier analysis revealed presence of 14 adaptive SNPs, out of which 5 were classified to be under decisive selection pressure. Notably, Jayanti rohu (JR) displayed 297 private alleles exclusive to its population. Chromosomes 7 and 16 emerged as potential hotspots containing a majority of the identified SNPs. Structure and principal component analysis revealed two distinct clusters, effectively distinguishing the JR and wild rohu populations. Phylogenetic analysis indicated a separate cluster of JR population distant from wild groups. CONCLUSION: The results of present study shall help in elucidating patterns of genetic variation and characterizing selection signatures associated with captive bred and natural populations of rohu. The genomic resources generated through this work shall be helpful in improving the traceability of selectively bred germplasm for developing future strategies of genetic management.

Pharmacogenetic analysis of interleukin-10 variants and tacrolimus metabolism in kidney transplant patients from Pakistani population.

BACKGROUND: End stage renal disease (ESRD) occurs when the kidneys are unable to filter the waste products and excessive fluids from the blood that results into the accumulation of toxins and fluid in the body. Tacrolimus is commonly used immunosuppressant while sirolimus and cyclosporin are rarely used drugs to stop solid organ transplant rejection. The host's immunological response following transplantation produces interleukin-10 (IL-10), which influences the varied CYP3A-dependent drug disposition of tacrolimus. The aim of this study was to determine the genetic polymorphisms of IL-10 (rs1800871, rs1800872 and rs1800896) gene associated with tacrolimus metabolism in kidney transplant patients from Lahore Punjab, Pakistan. METHODS: The study collected blood samples of 103 healthy individuals and 137 kidney transplant patients as control and treatment groups, respectively. We employed Tetra ARMS PCR for the genotype analysis of extracted DNA. The alleles were called on 2% agarose gel. Moreover, the study utilized SPSS software to analyze statistical significance of polymorphism. RESULTS: It was found that genotypic frequencies of IL-10 (rs1800871), IL-10 (rs1800872), and IL-10 (rs1800896) were (TT: 66.4%; TC: 31.4%; CC: 2.2%), (AA: 27.7%; AC: 54%; CC: 18.2%), (AA: 64.2%; GA: 17.5%; GG: 18.3%), respectively among kidney transplant patients. All parameters show significant association at different points after transplantation. Genetic analysis showed that TC and CC genotypes in rs1800871 (OR (95%CI) = 5.721 (3.231-10.131), P < 0.001; OR (95%CI) = 3.370 (0.642-17.672), P = 0.150), AC and CC genotypes in rs1800872 (OR (95%CI) = 1.294 (0.695-2.410), P = 0.415; OR (95%CI) = 1.453 (0.671-3.147), P = 0.342), GA and GG genotypes in rs1800896 (OR (95%CI) = 42.952 (17.566-105.021), P = 0.001; OR (95%CI) = 7.040 (2.563-19.333), P = 0.342) was associated with risk of renal rejection in kidney transplant patients. Besides, genetic models showed that TT in rs1800871, AA genotypes in rs1800872 and rs1800892 were associated with risk of renal rejection under dominant model when compared to controls (OR (95%CI) = 5.721 (3.231-10.131), P < 0.001; OR (95%CI) = 1.335 (0.735-9.290), P < 0.341; OR (95%CI) = 24.629 (10.599-57.230), P < 0.001), respectively. CONCLUSION: From the results, it is concluded that genetic polymorphism of IL-10 (rs1800871, rs1800872 and rs1800896) has a highly significant association with risk of renal rejection in Pakistani kidney transplant patients.

Association of histidine-rich glycoprotein C633T single nucleotide polymorphism and recurrent miscarriage in Iranian women.

BACKGROUND: Recurrent miscarriage (RM) is defined as the occurrence of at least two or three subsequent miscarriages within the 20th -24th weeks of pregnancy. The primary objective of this study was to investigate whether histidine-rich glycoprotein C633T single nucleotide polymorphism (HRG C633T SNP) statistically correlates with the occurrence of RM among Iranian women. METHODS AND RESULTS: Blood samples from 200 women were taken at the outset of the study. Then, the blood samples of 100 women who had a record of RM (case group) were compared with the other 100 women's blood samples who had no record of RM (control group). Following DNA extraction, the polymorphism of histidine-rich glycoprotein C633T (HRG C633T) for every case was specified and all women were genotyped by the amplification-refractory mutation system (ARMS) method. The results of the study revealed that there was a statistically significant difference between T/T genotype (OR = 3.5, CI (1.39-8.77), p = 0.007), and C/T genotype (OR = 1.83, CI (0.99-3.37), p = 0.05) in the case and control groups. Also, a statistically significant association was observed in T allelic frequency in the RM participants compared to the control group (OR = 2.01, CI (1.31-3.09), p = 0.01). CONCLUSIONS: The present study determined that there was a statistically significant relationship between HRG C633T SNP and increased RM regarding allelic and genotypical aspects. Moreover, it became apparent that women with homozygous T/T genotype were more susceptible to the risk of RM.

The association between endoplasmic reticulum aminopeptidase 2 gene single nucleotide polymorphisms and the risk of psoriasis and psoriatic arthritis in Egyptians.

BACKGROUND: Psoriasis (Ps) is a disorder attributed to the immune system that involves inflammation of the skin and joints. Psoriasis is a multifactorial disorder in which genetic factors represent about 70% of the disease risk. This study aims to establish the correlation between the ERAP2 gene's single nucleotide polymorphisms (SNPs) rs2910686 and rs2248374 with the susceptibility to Ps and/or psoriatic arthritis (PsA) among the Egyptian population. METHODS AND RESULTS: Genotyping of ERAP2 gene SNPs (rs2910686 and rs2248374) in 120 psoriatic patients with and without arthritis and 100 controls was done using real-time PCR. The genotype frequency and distribution of the ERAP2 SNP (rs2910686 and rs2248374) were in Hardy-Weinberg equilibrium (HWE). For rs2910686, the TC and CC genotypes and C allele frequency were significant risk factors for PsA compared to the controls (OR = 5.708, OR = 10.165, and OR = 4.282, respectively). They also were significant risk factors for Ps compared to the controls (OR = 5.165, OR = 5.040, and OR = 3.258, respectively). For rs2248374, the AG genotype significantly increased the risk of PsA (OR = 2.605) and Ps (OR = 3.768) compared to controls. The AG genotype was significantly related to the risk of Ps (OR = 3.369) G allele with PsA (OR = 1.608) and Ps (OR = 1.965) compared to controls. CONCLUSION: In Egyptian individuals, the ERAP2 gene polymorphisms (rs2248374 and rs2910686) may contribute genetically to the pathophysiology of psoriasis and PsA.

Molecular analyses of MEFV gene mutation variants in Turkish population.

BACKGROUND: Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disease primarily affecting individuals of Turkish, Armenian, Arab, and non-Ashkenazi Jewish descent, caused by mutations in the MEFV gene. The aim of this study was to review the common genotype distributions of MEFV variants and mutations in the Turkish population and evaluate rare mutations. METHODS AND RESULTS: The study included 2984 patients who applied to Ankara University Ibni Sina Hospital Immunology Laboratory with clinical suspicion of FMF between 2004 and 2014. The data of patients from different regions of the country who were followed up in the immunology-rheumatology clinic with clinical suspicion and presumptive diagnosis of FMF were evaluated retrospectively. Patients were tested for all mutations in Exon 2 and Exon 10, including M694V, M680I, M694I, V726A, E148Q and R202Q. There were 2504 patients with FMF variant. According to genotyping, R202Q (n = 1567, 39.2%) was the most common mutation. The most common co-variant was the R202Q/M694V genotype (n = 507, 16.98%). Allele frequencies for MEFV mutations were as follows: R202Q (n = 1567, 39.2%), M694V (n = 1004, 25.1%), E148Q (n = 463, 11.5%), M680I (n = 354, 8.8%), V726A (n = 319, 7.9%), A744S (n = 51, 1.2%), R761H (N = 41, 1.0%), P706P (N = 25, 0.6%), E167D (N = 23, 0.5%), M694I (N = 23, 0.5%), and K695R (N = 20, 0.5%). CONCLUSION: This research revealed the prevalence of both common and rare MEFV gene mutations in Turkish FMF patients in various age groups. R202Q was the most prevalent mutation.

Genotypic variation in CYP2E1, GCKR, and PNPLA3 among nonalcoholic steatohepatitis patients of Turkish origin.

BACKGROUND: This study examines genetic variations in CYP2E1 (rs6413432, rs3813867), GCKR (rs780094, rs1260326), and PNPLA3 (rs738409) among Turkish patients to assess their influence on nonalcoholic steatohepatitis. METHODS: Allele and genotype frequencies were compared between 245 NASH patients and 120 healthy controls using SNP genotyping via polymerase chain reaction-restriction fragment length polymorphism. Additionally, the deviation of the observed genotype frequencies from Hardy-Weinberg proportion was examined. RESULTS: No significant differences were found in the allelic and genotypic distributions of rs6413432, rs3813867, and rs780094 between NASH patients and healthy controls. However, significant disparities were noted for rs1260326 and rs738409. Gender and age-specific distributions showed no notable differences. The only observed deviation from Hardy-Weinberg proportion was in the genotype frequency of rs738409. CONCLUSIONS: Variants in GCKR (rs1260326) and PNPLA3 (rs738409) are significantly associated with increased NASH risk in the Turkish population, with the rs738409 variant potentially playing a more prominent role in NASH development.

Mannose-Binding Lectin Gene Variants as Disease Susceptibility Biomarkers in Rheumatoid Arthritis.

Background: Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease characterized by progressive destruction of peripheral joints. About 1% of the human population worldwide is suffering from this disease. The pathophysiology of RA is largely being influenced by immune dysregulation. Mannose-binding lectin (MBL), an acute-phase protein, has been reported to play an important role in pathogenesis of RA by the activation of complement pathway. Various studies documented the established the role of MBL in pathogenesis of various autoimmune diseases, including RA. MBL protein is encoded by gene MBL2, mapped on chromosome 10q11.2-q21. Objective: Both MBL serum levels and activity are mainly determined genetically by its variants. So considering the putative clinical role of MBL2, this case-control association study was designed to assess its six functional variants in a northwestern Indian cohort. Methods: Genetic typing of six MBL2 variants was done by amplification refractory mutation system-polymerase chain reaction. Data were analyzed using suitable statistical tools. Results: Significant difference has been observed in genotypic and allelic distribution between cases and controls for rs11003125. Comparison of allelic distribution for rs1800450 showed significantly high prevalence of A allele in cases than controls. Conclusion: These results indicate that MBL2 variants may act as plausible marker for susceptibility toward RA. Keeping this in view, it is pertinent to screen these variants in other population groups of India.

Association of interleukin6 rs1800796 gene polymorphism and serum level with bladder cancer in Egyptian population.

BACKGROUND: Urinary bladder cancer (UBC)is a common tumor of the urinary tract. OBJECTIVES: To assess the diagnostic significance of IL6 rs1800796 gene polymorphism and IL6 serum level among Egyptian patients with UBC. DESIGN AND METHODS: One hundred patients with UBC were selected from the Mansoura Urology and Nephrology Center, in addition to 100 healthy control subjects; using PCR and ELISA techniques for IL6 detection. RESULTS: The rs1800796 GC, CC genotypes, and C allele were significantly more prevalent in the cases with bladder cancer compared to the healthy group (p < 0.001, = 0.021, < 0.001 respectively). There was a clear association between elevated levels of IL6 and bladder cancer versus the control group (median = 4.2, 0.89 respectively, p < 0.001). Serum IL6 levels showed significantly higher levels in patients carrying CC, followed by GC then GG genotypes. No significant association was found between IL6 rs1800796 gene polymorphism or serum level with demographic or laboratory data. CONCLUSION: It is suggested that there is a clear link between elevated IL6 levels as well as IL6 rs1800796 gene polymorphism with bladder cancer, suggesting their potential utility as biomarkers for the disease.

Genetic association of the BsmI variant of vitamin D receptor gene with risk of morbid obesity.

OBJECTIVE: The aim of this study was to evaluate the vitamin D receptor (VDR) BsmI variant in morbidly obese patients compared with healthy normal controls. METHODS: The study included 103 patients with morbid obesity and 120 healthy individuals serving as normal controls. The DNA samples obtained from blood were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The gender, age, smoking status, triglycerides, total cholesterol, insulin, mean body mass index, and frequency of allele and genotype of the BsmI variant in the VDR gene in morbidly obese patients were evaluated. RESULTS: The body mass index of the patients was 47.14 ± 7.19. The VDR B/B, B/b, and b/b genotype frequencies were 27.2% versus 28.3%; 54.4% versus 50%; and 18.4% versus 21.7% in the morbidly obese patients and the control group, respectively. There was no statistically significant difference between patients and control subjects in the genotype and allele distribution of the VDR BsmI variant (p>0.05). Both patients and control genotype frequencies are consistent with Hardy-Weinberg equilibrium. CONCLUSION: The BsmI variant in the VDR gene may not seem to predispose to morbid obesity in our study population. Further studies with a larger number of subjects are needed to make a more precise evaluation of this relationship.

Association analysis of miRNA-146a and miRNA-196a polymorphism with breast cancer risk in Khyber Pakhtunkhwa, Pakistan: a preliminary study.

BACKGROUND: microRNAs (miRNAs) are small, noncoding RNA molecules, functioning either as oncogenes or tumor suppressor genes. SNPs in miRNAs might modify the expression of genes associated with miRNAs, enhancing susceptibility to breast cancer. Both miRNA-146a (rs2910164) and miRNA-196a (rs11614913) are identified and significantly associated with breast cancer risk in several ethnicities, but remains unexplored in Khyber Pakhtunkhwa population of Pakistan. METHODS: This study was aimed to check the relation of selected SNPs with breast cancer risk. The research cohort included 100 breast cancer patients and 100 healthy controls. All the participants were subjected for DNA extraction followed by T-ARMS PCR and gel electrophoresis. RESULTS: The results revealed a strong association between risk allele (G) of miRNA-146a and increased risk of breast cancer (OR = 2.04, P = 0.0006). Similarly, heterozygous and mutant genotypes also indicated high risk and significant association with breast cancer risk (CG; OR = 0.51, 9 P = 0.0001) (GG; OR = 3.76, P = 0.04). However, risk allele (T) of miRNA-196a (rs11614913) failed to exhibit significant association with breast cancer risk (OR = 0.92 P = 0.68). Similarly, the heterozygous and mutant genotype did not show significant association with breast cancer risk (CT; OR = 0.52, P = 0.125 (TT; OR = 0.88, P = 0.84). Furthermore, miRNA-146a (rs2910164) and miRNA-196a (rs11614913) polymorphisms exhibited non-significant associations with family history (P = 0.34, P = 0.77), PR status (P = 0.310, P = 0.397), ER status (P = 0.992, P = 0.981), nodal status (P = 0.86, P = 0.90), and menstrual status (P = 0.97, P = 0.09). Notably, miRNA-196a showed a significant association with the metastasis group (P = 0.010) and cancer stages (P = 0.047). CONCLUSIONS: In conclusion, this study highlights the association of miRNA-146a (rs2910164) polymorphism with breast cancer risk but suggested non-significant association of miRNA-196a (rs11614913) with breast cancer risk. However, these findings need to be confirmed through larger data set for more accurate result.