Polymorphism In Exon Research Articles

Severe toxicity in adult patients with lung cancer under treatment with pemetrexed: a prospective cohort study

Pemetrexed is an antimetabolite approved for treatment of non-small cell lung cancer. Harbouring interindividual variability in both the pharmacokinetic and pharmacogenetic profiles may lead to life-threatening toxicities. A prospective cohort study of adult patients initiating treatment with pemetrexed in combination with platinum between 2013 and 2015 were follow up. Primary exposure were the methylenetetrahydrofolate reductase (MTHFR) single base polymorphisms in exon 4 and 7 and 5'-UTR- thymidylate synthase (TYMS) VNTR genotypes, in addition to baseline clinical and demographic variables. We used a Cox regression model to evaluate patient's survival and toxicity experience and its association with both baseline characteristics, and a-priori determined genetic polymorphisms. Seventy two patients were included, 52.7% developed severe hematologic toxicity during follow-up. None of the tested genotypes were significantly associated with the main outcome on multivariate analysis, nor other basal clinical variables. Overall survival between patients experiencing the outcome was not different from those without it, but hospital admissions were more frequent. MTHFR and 5'-UTR-TYMS genotypes were not useful for predicting high grade toxicity events in patients under treatment with pemetrexed.

Norrie disease gene polymorphism in Indonesian infants with retinopathy of prematurity

ObjectiveRetinopathy of prematurity (ROP) is a major cause of blindness in newborn infants, which also occurs in low-income and middle-income countries. Why ROP progresses in some infants while it regresses...

Angiotensin II type 2 receptor gene polymorphisms and serum angiotensin-converting enzyme level in Egyptian children with systemic lupus erythematosus.

There are no reports about the association of angiotensin II type 2 receptor ( AT2R) gene polymorphisms and susceptibility to systemic lupus erythematosus (SLE) in children. The objective of this research is to study AT2R gene polymorphisms in exon 3 (C1593A) and intron 1 (A1675G) in Egyptian children with SLE and its correlation with disease manifestations and serum angiotensin-converting enzyme (ACE) level. Typing of AT2R gene polymorphisms was conducted in 123 children with SLE in comparison with 100 healthy controls using the restriction fragment length polymorphism method. Significant differences were found between SLE patients and controls for A-containing genotypes (CA + AA) and A-allele frequencies of AT2R in exon 3 (C1593A) ( p = 0.01, odds ratio (OR) = 2.5, 95% confidence interval (CI) = 1.3-5.05; p = 0.01, OR = 2.2, 95% CI = 1.2-4.1, respectively). G-containing genotypes (AG + GG) and G allele of AT2R in intron 1 (A1675G) were more frequent in SLE patients compared to controls ( p = 0.01, OR = 2.3, 95% CI = 1.2-4.5; p = 0.02, OR = 2.1, 95% CI = 1.2-3.7, respectively). Serum ACE level was significantly higher in SLE patients than in controls ( p < 0.001). There was no association between AT2R gene polymorphisms and ACE level in serum. Moreover, there was no association between AT2R gene polymorphisms and SLE clinical manifestations. AT2R gene polymorphisms can be considered risk factors for SLE development in Egyptian children.

Polymorphisms in Exon-1 and Partial Intron-1 of Growth Hormone Gene and its Association with Body Weight Traits in Broiler

Polymorphisms in Exon-1 and Partial Intron-1 of Growth Hormone Gene and its Association with Body Weight Traits in Broiler

Genetic effects of leptin receptor (LEPR) polymorphism on litter size in a Black Bengal goat population

Abstract The leptin receptor (LEPR) is involved in central signaling for both energy homeostasis and reproduction. The present study investigates the association of the LEPR gene with the prolificacy of Black Bengal goat. Two single nucleotide polymorphisms (SNPs) in intron 3 and one SNP in exon 4 in the LEPR gene were identified by pooled DNA sequencing. The identified SNPs were genotyped by the direct sequencing method from 84 Black Bengal does. A synonymous mutation (Lysine &gt; Lysine) was found as a polymorphism in exon 4. The effects of the different genotypes on litter size traits were estimated using linear models. Our results show that goats with heterozygous genotype AG at the loci g.104911A&gt;G and g.105151A&gt;G showed the highest prolificacy performance when compared with the other, homozygous genotypes. Dominance and additive effects were observed at the considered loci. No significant allele substitution effects were found for any locus. Our results indicate preliminarily that LEPR may have some association with prolificacy and could be a candidate gene to improve the prolificacy in goat.

Pedigree analysis for the rare RHD DVa allele: serological and molecular studies

Until now, worldwide more than 80 different alleles producing weak D phenotypes have been identified. Here we identified rare RHD DVa alleles in Chinese individuals associated with weak expression of D antigen and an RHD phenotype resembling DVI. Multi-monoclonal anti-D antibodies were used to identify the RHD phenotyping for rare RHD DVa. RHD genotyping was used to confirm the presence of RHD exons and identify RHD, RHCE hybrids and exon deficiencies. Sanger sequencing was used to identify nucleotide polymorphisms in RHD exons. Pedigree analysis demonstrated RHD DVa allele alterations of 667 T>G, 676 G>C, 697 G>C, 712 G>A, 733 G>C, 744 C>T and 1227 G>A, which means the proband's alleles were RHD DVa-3 [also called RHD-CE(5)-D] and 1227 G>A. The results also demonstrated RHD DVa and the original RHD Va allele without 1227 G>A. The study suggests that RHD phenotyping is a superior strategy for the molecular analysis of RHD variant in Chinese subjects, and for understanding related polymorphisms and mutations.

Genetic polymorphism in DNA base excision repair gene XRCC1among medical radiation workers

X-rays repair cross-complementing group 1 (XRCC1) gene is one of the gene that plays an important role in base excision repair system (BER) and DNA repair both single and double strand breaks. Individuals with XRCC1 exon 10 (Arg399Gln) gene polymorphisms and carrying 399Gln allele variants (A allele) have a greater risk of DNA damage than their wildtype, 399Arg. The aim of this study was to examine the genotype frequencies of single nucleotide polymorphisms (SNPs) of XRCC1 exon 10 among medical radiation workers. This study involved 77 samples from several hospitals in Indonesia. Genotyping of XRCC1 exon 10 gene polymorphism was performed using PCR-RFLP. Individuals carryingA allele had lower frequency than that is carrying their wildtype of 399Arg (0.39 vs. 0.61). The results indicated that 39% of medical radiation workers had a risk of repair efficiency of DNA damage and might influence an individual's risk of cancer. Ionizing radiation induces many types of damage to DNA, requiring multiple repair pathways to restore genomics integrity. Other important genes/pathways, especially those for DNA double-strand break repair, might also play a role and should be further investigated. Furthermore, polymorphisms leading to inefficient DNA repair might also be associated with late reactions to radiotherapy.

The Effect of HER2 Single Nucleotide Polymorphisms on Cervical Cancer Susceptibility and Survival in a Chinese Population.

Background: Cervical cancer (CCa) is a multifactorial gynecologic disease worldwide. Effects of HER2 polymorphisms, especially those in exonic region, have been investigated in many gynecologic diseases. In this study, we evaluated the influence of functional HER2 polymorphisms on susceptibility and survival of CCa in a Chinese population.Methods: We genotyped the HER2 exonic polymorphisms by TaqMan in both case-control study (413 CCa patients vs. 396 controls) and survival study (413 CCa patients). Logistic regression and Cox regression were adopted to evaluate the genetic association with the risk and outcomes of CCa, respectively.Results: In the case-control study, there was no significant difference between patients and controls in either HER2 rs1136201 or rs1058808. However, when combined, these two polymorphisms demonstrated a significant hazardous effect for CCa (P = 0.012). Besides, number of variants was also influential (P trend =0.002). In survival analysis, dominant model of rs1136201 and co-dominant modelof rs1058808 were significantly associated with the survival (P = 0.037 and P =0.028). The combination of rs1136201 and rs1058808 also negatively impacted CCa survival (P = 0.009). Cox regression further revealed the significance of the polymorphism combination (β = 0.38, P = 0.025, HR= 1.47, 95%CI = 1.05-2.05). Functional assay of these polymorphisms demonstrated that rs1058808 G allele was associated with stronger expression of HER2 gene.Conclusions: Our results suggested that the combination of HER2 rs1136201and rs1058808 was significantly associated with the susceptibility of CCa. Besides, this combination of polymorphism s also substantially impacted the survival of CCa patients.

Influence of Caspase-9 polymorphisms on the development of Chronic Myeloid Leukemia- A case-control study.

IntroductionChronic Myeloid Leukemia (CML) is a myeloproliferative disorder, characterized by the overproduction of myeloid cells in all stages of maturation. It is usually defined by three sequential stages (Chronic, Accelerated and Blast-crisis) where the transition from chronic to accelerated to blast phases is presumed to occur due to secondary genetic changes, viz. accumulation of mutations, activation of downstream pathways and failure of apoptosis. Caspase 9 is the initiator caspase involved in mitochondrial-mediated apoptotic pathway. Polymorphisms in the promoter (−1263 A>G, -712C>T, -293 del) and coding (Ex5 +32G>A) regions of CASP9 gene are found to influence the expression levels by either impairing the activation or loss of expression of CASP9 or insufficient formation of apoptosome.MethodsThe present case-control study was carried out on 999 individuals, comprised of 485CML cases reported at Nizams Institute of Medical Sciences (NIMS), Hyderabad and 514 age and gender-matched healthy individuals from local population. DNA was isolated by non-enzymatic/salting-out method and was genotyped using RFLP technique.ResultsIt was observed that the presence of G allele of CASP9 -1263A>G polymorphism enhanced the risk for CML while CASP9 -712C>T and CASP9 -293del SNPs conferred protection against development of CML. Haplotype analysis of promoter and exonic polymorphisms had revealed increased risk associated with two haplotypes G_C_del (+)_G (OR-1.61, 95% CI-0.97-2.65, p-0.06#) and G_C_del (–)_G (OR-2.09, 95% CI-0.94-4.66, p-0.07#) suggesting the role of G allele of CASP9 -1263A>G in conferring risk independent of other SNPs. Pairwise LD analysis performed for all the four SNPs revealed the presence of LD among the SNPs.ConclusionThe results of the present study therefore concludes the role of CASP9 -1263A>G polymorphism in increasing the risk for the development and progression while CASP9 -712C>T and CASP9 -293del SNPs conferred protection and CASP9 Ex5 +32G>A was involved in conferring resistance which could be in combination with other SNPs or factors affecting them.

ANALYSIS OF CANDIDATE POLYMORPHISMS AT EPILEPSY PATIENTS WITHOUT MECHANICAL DISTURBANCES

Thе article presents the results of a molecular-genetics research on patients with diagnosed epilepsy without mechanical disturbance. The aim of this research was the analysis of candidate gene polymorphisms in development of different forms of epilepsy excepting mechanical reasons. 78 patients of V.M. Savinov SVS clinic with different forms of epilepsy were selected for the molecular-genetic analysis. Genotyping on candidate polimorphisms of gene coding the methyl-СрG-binding protein 2 (МЕСР2, 3 polymorphisms), the genes of sodium (SCN1A, 4 polymorphisms) and potassium (KCNT1, 2 polymorphisms) channels was performed by a site-specific PCR-RFLP method. Molecular genetic analysis revealed the presence of normal functioning alleles for 3 investigated candidate polymorphisms (p.Thr158Met, p.Thr197Met, p.Arg306Ter) of 3d exon of МЕСР2 gene at all epilepsy patients. However, 1 case (patient suffering from Dravet syndrome) of de novo mutation was defined for sodium channel gene (SCN1A p.Ala1783Thr) and 3 cases (2 patients suffering from temporal epilepsy and 1 patient with residual encephalopathy) of new mutations in gene responsible for potassium channel (KCNT1 p.Ala934Thr). To determine the inherited SCN1A and KCNT1 mutations, the molecular-genetics analysis was conducted for close relatives of patients. As a result, we conclude that, candidate polymorphisms of SCN1A p.Ala1783Thr and KCNT1 p.Ala934Thr, disrupting the ion channels normal functioning, can be involved in development of non-mechanical forms of epilepsy.

Nutrigenomics and Nutrigenetics in Functional Foods

The main function of the diet is to provide the necessary nutrients to meet the nutritional needs of people. Since long, there is evidence that there is a relationship between diet and health and from these arose the concept of functional foods. In general, functional foods are those that not only fulfill a nutritional function but also contain biologically active components that offer health benefits and reduce the risk of suffering diseases. An important key to know the effect that functional foods have on nutrition is to determine how the body responds to the stimulation of these. In other words, the components of the diet can alter genomic expression. However, not all people respond in the same way. A large number of genes from the human genome are induced to code for the proteins involved in the nutritional processes and the induction of these genes is determined by the polymorphisms that each person has in their genome. For example, a diet rich in folic acid prevents the development of cardiovascular diseases related to people who have a polymorphism in exon 4 of the MTHFR gene related to folate metabolism. Therefore, the proposal of this book is to review the current research of Nutrigenomics, which is the study of the effect of nutrients on the expression of genes and Nutrigenetics which is the influence of polymorphisms of people in response to nutrients.

Association of functional polymorphisms in 3'-untranslated regions of COMT, DISC1, and DTNBP1 with schizophrenia: a meta-analysis.

In recent years, various studies have accumulated evidence of the involvement of single nucleotide polymorphisms (SNPs) in introns and exons in schizophrenia. The association of functional SNPs in the 3'-untranslated regions with schizophrenia has been explored in a number of studies, but the results are inconclusive because of limited meta-analyses. To systematically analyze the association between SNPs in 3'-untranslated regions and schizophrenia, we conducted a meta-analysis by combining all available studies on schizophrenia candidate genes. We searched candidate genes from the schizophrenia database and performed a comprehensive meta-analysis using all the available data up to August 2017. The association between susceptible SNPs and schizophrenia was assessed by the pooled odds ratio with 95% confidence interval using fixed-effect and random-effect models. A total of 21 studies including 8291 cases and 9638 controls were used for meta-analysis. Three investigated SNPs were rs165599, rs3737597, and rs1047631 of COMT, DISC1, and DTNBP1, respectively. Our results suggested that rs3737597 showed a significant association with schizophrenia in Europeans (odds ratio: 1.584, P: 0.002, 95% confidence interval: 1.176-2.134) under a random-effect framework. This meta-analysis indicated that rs3737597 of DISC1 was significantly associated with schizophrenia in Europeans, and it can be suggested as an ethnic-specific risk genetic factor.

Genome-wide meta-analysis identifies 3 novel loci associated with stroke.

We conducted a European‐only and transancestral genome‐wide association meta‐analysis in 72,147 stroke patients and 823,869 controls using data from UK Biobank (UKB) and the MEGASTROKE consortium. We identified an exonic polymorphism in NOS3 (rs1799983, p.Glu298Asp; p = 2.2E‐8, odds ratio [OR] = 1.05, 95% confidence interval [CI] = 1.04–1.07) and variants in an intron of COL4A1 (rs9521634; p = 3.8E‐8, OR = 1.04, 95% CI = 1.03–1.06) and near DYRK1A (rs720470; p = 6.1E‐9, OR = 1.05, 95% CI = 1.03–1.07) at genome‐wide significance for stroke. Effect sizes of known stroke loci were highly correlated between UKB and MEGASTROKE. Using Mendelian randomization, we further show that genetic variation in the nitric oxide synthase–nitric oxide pathway in part affects stroke risk via variation in blood pressure. Ann Neurol 2018;84:934–939

CD33 SNP Genotype and Splice Variation Are Associated with CD33 Cell Surface Expression and SGN-CD33A Pharmacokinetics

The cell surface antigen CD33 is expressed on the majority of AML blasts and is appropriate for immunotherapeutic targeting with antibody drug conjugates (ADCs). Expression of CD33 is in part mediated by splicing of the CD33 transcript, and has been demonstrated to be one of the factors that may mediate response to the ADC gemtuzumab ozogamicin, which results in significant benefit in some patients but lacks responses in others. Splicing of the CD33 transcript is in part regulated by a single nucleotide polymorphism (SNP) in exon 2 (e2) that causes a C>T substitution and the resultant skipping of e2. CD33 thus exists in 2 main isoforms, as either a full length (FL) transcript or a truncated version missing e2 (Δe2), which includes the IgV binding domain that is the epitope for diagnostic and therapeutic antibodies (Ab). The CC genotype encodes the FL isoform at a higher rate compared to the CT or TT, and the TT genotype encodes the short isoform at a higher rate compared to CT or CC. SGN-CD33A is a CD33-directed ADC, utilizing a pyrolobenzodiazepine (PBD) dimer. SGN-CD33A has been evaluated in multiple clinical trials as either monotherapy or in combination. We hypothesized that the patient's CD33 genotype would impact CD33 expression as well as response characteristics following treatment with SGN-CD33A.We analyzed CD33 genotype variation in bone marrow (BM) or peripheral blood (PB) samples from patients treated with SGN-33A as either monotherapy (NCT01902329; n=133) or in combination with hypomethylating agents (HMAs; NCT02785900; n=83). CD33 SNP genotyping was determined on gDNA using RFLP PCR with 2 restriction enzymes recognizing cut sites generated by the C and T polymorphisms and genotype confirmed using fragment length analysis (CC=108, CT=86, TT=22). CD33 surface expression on the AML blasts was determined by flow cytometric analysis using the human anti-CD33 monoclonal Abs HIM3-4 and H212, which bind to the membrane-proximal C2-set and V-set domain, respectively. HIM-34 measured CD33 levels independent of SNP-driven splice variation. The h2H12 epitope is within e2, thus its binding may be susceptible to splice variation. We subsequently evaluated the association of CD33 genotype with pharmacokinetic (PK), clinical and other variables using a generalized regression model.Patients classified as CC genotype had significantly higher surface CD33 expression as determined by flow cytometry in both BM and PB. In accordance with observed differences in CD33 expression, we also found drug exposure demonstrated an inverse relationship according to CC genotype in both mono and combination therapy trials. For monotherapy, compared to patients with CC and CT genotypes, patients with TT genotypes had significantly higher drug exposure following SGN-CD33A. Patients with TT had higher AUCs following the first and last doses of SGN-33A (p < 10-4 -; Fig 1). Cmax following SGN-CD33A exposure was higher in TT genotype patients compared to the CT and CC (p< 10-1.5 for Cmax following the first dose and p<10-1.6 for Cmax over all treatments;Fig 1). In combination with HMAs, the TT genotype was also associated with significantly higher SGN-CD33A AUC and Cmax (p-values ranging from 10-3.3 - 10-9.7).We next examined expression and subcellular localization of CD33 to elucidate the mechanism by CD33 variation contributes to cell surface presentation. Transfection of cDNA encoding the FL CD33 transcript resulted in increased cell surface expression, as indicated by flow cytometry with both HIM3-4 and h2H12. In contrast, both Abs failed to detect cell surface CD33 following transfection with cDNA encoding the Δe2 variant. Examination of the intracellular compartment revealed that HIM3-4, but not 2H12, binds to the Δe2 variant in a pattern localized proximal to the nucleus. Taken together, our findings suggest that the Δe2 splice CD33 variant lacks the portion of the V-set domain required for h2H12/SGN-CD33A binding and does not efficiently traffic to the cell surface. We show that CD33 SNP genotype is associated with CD33 expression, with CC patients demonstrating higher CD33 as detected by flow cytometry; and that CD33 SNP genotype affects the PK profile of SGN-CD33A, with TT patients having higher levels of drug exposure. Our findings suggest that the CD33 genotype can impact CD33 expression, PK profile, and trafficking of bound agents and thus may impact therapeutic targeting of CD33-directed agents. [Display omitted] DisclosuresWang:Seattle Genetics: Employment, Equity Ownership. Rohm:Seattle Genetics: Employment, Equity Ownership. Biechele:Seattle Genetics: Employment, Equity Ownership. Means:Seattle Genetics: Employment, Equity Ownership. Thurman:Seattle Genetics: Employment, Equity Ownership. Arthur:Seattle Genetics: Employment, Equity Ownership.

BIM deletion polymorphism accounts for lack of favorable outcome in Japanese females with follicular lymphoma

Deletion polymorphism of BCL-2-like protein 11 (BIM) is specifically found in East Asia. To explain some epidemiological discrepancies between Asian and Western countries, we analyzed a silent single nucleotide polymorphism (SNP) in exon 5 (c465C > T) and a deletion site (2903 bp) in intron 2 in 77 patients with follicular lymphoma by the Q-invader method using PCR. In females, 5-year progression-free survivals (PFS) were 20.0% in the BIM deletion group, 66.7% in the SNP group and 81.5% in the wild-type (WT) group (p = .0012). In the WT group, 5-year PFS was 40.4% in males (p = .0448 vs. female PFS). This tendency was strengthened in patients receiving rituximab (26.9% vs. 84.2%, p = .006). Superior PFS in the WT females in Japan was comparable with the results of cohort studies in the United States and Sweden. Favorable prognosis in Japanese females may be masked by the BIM deletion polymorphism.

Analysis of the KCNQ1 gene mutation in 2 families with congenital long QT syndrome type 1 in Xinjiang Uygur Autonomous Region

Objective: Present study analyzed the association betwen the postassium voltage-gated channel KQT-like subfamily member 1 gene (KCNQ1) mutation and the clinical and the electrocardiographic features in 2 pedigrees with congenital long QT syndrome type 1 (LQT1) in Xinjiang Uygur Autonomous Region. Methods: Three family members were diagnosed as LQT1 patients in 2 Uygur congenital LQT1 families, these 3 LQT1 patients served as long QT group, 24 Uygur healthy volunteers served as control group. Electrocardiogram (ECG) and the gene detection were applied to compare the ECG and molecular genetic features between the long QT group and control group, and to explore the relationship between the KCNQ1 gene mutation and the clinical and the electrocardiographic features in these 2 families with congenital long QT syndrome type 1. Results: The LQT1 was diagnosed in 3 cases of the 2 pedigrees. The common features of ECG were QTc>480 ms, prolonged ST segment, and delayed T wave. The gene test evidenced a polymorphism of KCNQ1 gene exon 13:47G➝A(R16R). The mutation of 133G➝A9(G45S) of exon 16 resulted in the change of the original glycine (G) to serine (s). The ECG of the control group were normal, and there were no KCNQ1 gene mutations in control group. Conclusion: The exon sequencing results of KCNQ1 gene in 2 Xinjiang Uygur congenital long LQT1 families showed that exon16 missense changes (133G to A (G45S)) can lead to amino acid mutation, this mutation may be a pathogenic mutation. Subsequent validation of the expanded sample will provide a reference for revealing the relationship between the KCNQ1 gene and the pathogenesis of LQT1.

An IL7RA exon 5 polymorphism is associated with impaired IL-7Rα splicing and protection against tuberculosis in Ghana

Functional interleukin-7 receptor α-chain (IL-7Rα) genetic variants, which affect alternative splicing and expression of the soluble IL-7Rα, are associated with susceptibility to autoimmunity. We previously described aberrant IL-7Rα expression and impaired IL-7-mediated T-cell functions in tuberculosis patients. In the present study, we investigated a possible role of IL7RA gene variants. Six exonic IL7RA polymorphisms were genotyped and two minor alleles were found at lower frequencies in tuberculosis patients as compared to healthy contacts from Ghana (rs11567764, p = 0.002; rs1494558, p = 0.01). The rs11567764 polymorphism tags an IL7RA haplotype exclusively found in African populations and was predicted to affect splicing of exon 5. Reduced mRNA expression of the Δexon_5-6 variant was found in T-cells from carriers of the protective rs11567764 allele. Although we were not able to demonstrate the causative effect of rs11567764, our findings suggested functional implications of genetic variants on IL-7Rα splicing and with potential impact on T-cell protection against tuberculosis.

Playing Hide-and-Seek in Beta-Globin Genes: Gene Conversion Transferring a Beneficial Mutation between Differentially Expressed Gene Duplicates.

Increasing evidence suggests that adaptation to diverse environments often involves selection on existing variation rather than new mutations. A previous study identified a nonsynonymous single nucleotide polymorphism (SNP) in exon 2 of two paralogous β-globin genes of the bank vole (Clethrionomys glareolus) in Britain in which the ancestral serine (Ser) and the derived cysteine (Cys) allele represent geographically partitioned functional variation affecting the erythrocyte antioxidative capacity. Here we studied the geographical pattern of the two-locus Ser/Cys polymorphism throughout Europe and tested for the geographic correlation between environmental variables and allele frequency, expected if the polymorphism was under spatially heterogeneous environment-related selection. Although bank vole population history clearly is important in shaping the dispersal of the oxidative stress protective Cys allele, analyses correcting for population structure suggest the Europe-wide pattern is affected by geographical variation in environmental conditions. The β-globin phenotype is encoded by the major paralog HBB-T1 but we found evidence of bidirectional gene conversion of exon 2 with the low-expression paralog HBB-T2. Our data support the model where gene conversion reshuffling genotypes between high- and low- expressed paralogs enables tuning of erythrocyte thiol levels, which may help maintain intracellular redox balance under fluctuating environmental conditions. Therefore, our study suggests a possible role for gene conversion between differentially expressed gene duplicates as a mechanism of physiological adaptation of populations to new or changing environments.

Association between XRCC1 exon 10 (Arg399Gln) gene polymorphism and micronucleus as a predictor of DNA damage among radiation workers

Surniyantoro HNE, Lusiyanti Y, Rahardjo T, Nurhayati S, Tetriana D. 2018. Association between XRCC1 exon 10 (Arg399Gln) gene polymorphism and micronucleus as a predictor of DNA damage among radiation workers. Biodiversitas 19: 1676-1682. This study was aimed to examine the association between XRCC1 exon 10 gene polymorphism and micronucleus frequencies in radiation workers and their relation to the confounding factors. This study involved 37 radiation workers and 37 controls from several hospitals in Indonesia. Genotyping of X-ray cross-complementing group 1 (XRCC1) exon 10 gene polymorphism and micronucleus assay were performed using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and Cytokinesis-Block Micronucleus assay (CBMN assay), respectively. The results indicated that MN frequencies were not significantly higher in the exposed workers than in controls (20.46±6.42 versus 16.89 ±9.72; P=0.07). The micronucleus frequencies of radiation workers with mutant genotype showed not significantly higher than controls in the same genotypes (22±6.64 versus 11.75 ± 8.13; P=0.11). The confounding factors, like age, years of employment and equivalent doses were significantly associated with micronucleus frequencies (P&lt;0.05). The equivalent dose has a significantly positive correlation with micronucleus frequencies among radiation workers, increasing the MN frequencies by 16.3 per 1 mSv of equivalent dose (P=0.001). The genetic polymorphism of XRCC1 gene exon 10 demonstrated no association with the extent of DNA damage in the hospital radiation workers. The MN frequencies were strongly associated with age, equivalent dose and years of employment.

Association of CD1 and FcγR gene polymorphisms with Guillain-Barré syndrome susceptibility: a meta-analysis.

CD1 and immunoglobulin G Fc receptor (FcγR) genes have been proposed to be involved in the pathogenesis of Guillain-Barré syndrome (GBS). However, results of different studies are conflicting. This meta-analysis aimed to systematically examine the association between CD1 and FcγR gene polymorphisms and GBS. A comprehensive literature search through PubMed, EmBase, ScienceDirect, and Cochrane Library was performed to identify all eligible studies. The strength of association was assessed by pooled odds ratios (ORs) and corresponding 95% confidence intervals (95% CI) in allelic, dominant, recessive, homozygous and heterozygous genetic models. Four case-control studies about polymorphisms of exon 2 in CD1A and CD1E genes and GBS risk and five studies (six cohorts) about FcγR gene polymorphisms and GBS risk were included in this meta-analysis. The association between exon 2 of CD1E gene polymorphism and GBS was marginally significant in Caucasians in allelic model (OR = 1.193, 95% CI = 1.001-1.423, P = 0.049). FcγRIIA gene polymorphism was significantly associated with GBS risk in Caucasians under allelic model (OR = 1.553, 95% CI = 1.018-2.368, P = 0.041) and dominant model (OR = 1.320, 95% CI = 1.027-1.697, P = 0.030). However, no significant association was found between polymorphisms in exon 2 of CD1A, FcγRIIIA and FcγRIIIB genes and GBS susceptibility. This meta-analysis suggested that FcγRIIA gene polymorphism may contribute to GBS risk in Caucasians and revealed a certain trend toward significance in the association of exon 2 of CD1E gene with GBS in Caucasians. Further studies with larger sample size are required to validate these results.