PstI Polymorphism Research Articles

Microsatellite diversity and restriction enzyme-based polymorphisms of MHC loci in native Turkish goats

Playing a key role in immunity and autoimmunity, Major Histocompatibility Complex (MHC) contains microsatellite regions and polymorphisms associated with resistance to several diseases and thermo-physiologic characteristics in farm animals. The aims of this study were ı) to estimate genetic diversity and phylogenetic relationships via 5 different MHC-linked microsatellite markers (BF1, BM1818, BM1258, SMHCC1 and DYMS1) and ıı) to assess restriction ezyme-based (PstI, TaqI, BsaHI and AluI) polymorphisms of MHC Class II-DRB gene in native Turkish goats. Based on MHC-linked microsatellite markers, number of alleles ranged from 8.20 (NRD) to 8.80 (HAI and KBK) across studied goat populations. Observed heterozygosity was between 0.68 (NRD) and 0.80 (KBK), whereas expected heterozygosity ranged from 0.74 (NRD) to 0.82 (KBK) in native Turkish goats. Inbreeding coefficients were 0.04, 0.13, -0.01 and 0.09 for HAI, HNM, KBK and NRD populations, respectively. A 284 bp length PCR products belonging to MHC Class II-DRB gene region were digested separately with PstI, TaqI, BsaHI and AluI restriction endonucleases to assess polymorphism status together with Hardy-Weinberg equilibrium in studied goat populations. P allele frequency ranged from 0.73 (KBK) to 0.95 (NRD), while p allele frequency was between 0.05 (NRD) and 0.27 (KBK) in PstI polymorphism. The highest and lowest frequency of T allele were detected in HNM (0.80) and KBK (0.49), respectively, whereas frequency of t allele was between 0.20 (HNM) and 0.51 (KBK) in TaqI polymorphism. G and A allele frequency were between 0.16 (HNM) - 0.39 (HAI) and 0.84 (HNM) – 0.61 (HAI), respectively in BsaHI polymorphism, while unexpected genotype patterns were observed in AluI polymorphism. In this study, high genetic diversity and low inbreeding were detected in native Turkish goats according to MHC-linked microsatellite markers. Additionally, presence of genotypes previously reported to be associated with tuberculosis resistance and heat tolerance were observed in native Turkish goat populations. Nevertheless, association analysis between these genotypes and tuberculosis resistance and heat tolerance should be confirmed in native Turkish goats.

Relationship between Pst-I polymorphism of mucin 4 gene and primary hepatolithiasis

Objective To investigate the relationship between Pst-I polymorphism of mucin 4 gene and primary hepatolithiasis in the Chinese population. Methods Venous blood of 96 healthy controls and 56 patients with hepatolithiasis were collected, and DNA was extracted. Polymerase chain reaction combined with restriction enzyme (PCR-RFLP) digestion was used to detect Pst-I polymorphism of mucin 4 gene in the two groups. The genotype and gene frequency between the two groups were then compared. Results The genotype frequencies of GC, GT, TT in the control and the hepatolithiasis groups were 21.3%, 12.7%, 55.6% and 53.2%, 41.2%, 19.8%, respectively. The alleles C and T gene frequencies in the control and the hepatolithiasis groups were 21.5%, 72.7% and 66.3%, 30.2%, respectively. There were significant differences in Pst-I polymorphism of mucin 4 genotype frequency and gene frequency between the two groups. Conclusion The data showed Pst-I polymorphism of mucin 4 gene was associated with primary hepatolithiasis in Chinese patients. Key words: Mucin 4; Pst-I polymorphism; Hepatolithiasis

CYP genetic variants and toxicity related to anti-tubercular agents: a systematic review and meta-analysis

BackgroundTreatment with anti-tuberculosis drugs may cause patients to experience serious adverse effects. Genetic factors, such as polymorphisms of CYP genes, may increase the likelihood of a patient experiencing such adverse drug reactions. In this systematic review and meta-analysis, we synthesised evidence for associations between CYP genetic variants and anti-tuberculosis drug-related toxicity outcomes.MethodsWe searched MEDLINE, PubMed, EMBASE, BIOSIS and Web of Science to identify relevant studies. We performed meta-analyses to obtain an effect estimate for each genetic variant on each outcome, and stratified all analyses by country. We qualitatively assessed the methodological quality of the included studies.ResultsWe included data from 28 distinct cohorts of patients in the review. We identified many areas of concern with regard to the quality of included studies. Patients with homozygous mutant-type or heterozygous genotype at the CYP2E1 RsaI polymorphism were significantly less likely to experience hepatotoxicity than patients with homozygous wild-type genotype (odds ratio [OR] = 0.75, 95% confidence interval [CI] 0.56–1.00; p = 0.047, I2 = 58.2%). No significant differences were observed for the CYP2E1 DraI and PstI polymorphisms. For the 96-bp deletion-insertion single-nucleotide polymorphism (SNP) of the CYP2E1 gene, homozygous mutant-type significantly increased hepatotoxicity risk compared with homozygous wild-type (OR = 8.20, 95% CI 1.38–48.68, I2 = 0%); no significant difference was observed for heterozygous genotype compared with homozygous wild-type (OR = 0.77, 95% CI 0.19–3.21, I2 = 0%).ConclusionsGenerally, we identified that coverage of the association between SNPs of CYP genes and anti-tuberculosis drug-related toxicity outcomes is incomplete. We observed significant associations between the RsaI and 96-bp deletion-insertion SNPs of the CYP2E1 gene and anti-tuberculosis drug-related hepatotoxicity. We were unable to comment on the impact of ethnicity on the investigated associations, as information on participants’ ethnicity was sparsely reported in the included studies.Systematic review registrationPROSPERO registration number: CRD42017068448.

Molecular Characterization of Insulin Gene in Diabetic Foot Ulcer Patients: A Pilot Study from Bengal Bay Coastal Origin

Objective: Many studies have showed that foot ulcer is the most frequent occurrence among diabetic patients in the south Indian origin. This study aimed to investigate on the hypothesis that in patients with diabetic foot ulcer in south Indian subjects there is a substitution within nucleotide sequence of coding region related to insulin gene and this may be signifying a link disequilibrium with the class III allele in the insulin gene locus, which can be considered due to its relevance with diabetes. We aim to examine this part of insulin gene to find out if there is any mutation within the insulin gene sequence that is relevant with diabetes mellitus. Materials and Methods: We used the PCR products of the amplified insulin gene from 40 patients diagnosed with foot ulcer seeking mutations, which might be in association with the class III allele and therefore indicates its relevance with the manifestation of diabetic foot ulcers. Results: We identified a β-chain mutant (i.e. insulin Chicago) using the restriction enzyme (MboII) in individuals afflicted with foot ulcer. A couple of patterns (α and β) were found indicating the presence of PstI polymorphism within the 3' un-translated part of the insulin gene. Besides, allele frequencies in subjects homozygous for α allele, homozygous for β allele and heterozygous were respectively 0.3 (12/40), 0.125 (5/40) and 0.575 (23/40). No significant variant regarding allelic frequency was characterized between the patients and normal controls, though a mutation in B-chain (insulin Chicago) was observed. Conclusion: Despite linkage disequilibrium between this polymorphism in the 3' un-translated portion of the insulin gene and the class III allele, it is unlikely to have advantage than the class III allele itself on prognosticating diabetes.

CYP2E1 PstI polymorphism increases cervical neoplasia risk: a meta-analysis.

Cytochrome P4502E1 (CYP2E1) is a key enzyme in the metabolic activation of many carcinogens, but the roles of CYP2E1 polymorphisms in cervical neoplasia (CN) are inconclusive. Published case-control cohort studies from the Pubmed, Embase, and China National Knowledge Infrastructure databases were retrieved. Data were extracted and pooled odds ratios with 95% confidence intervals were calculated. Seven studies examining 1097 cases and 1117 controls were included in this meta-analysis. The pooled effect size showed no association between CYP2E1 RsaI and DraI polymorphisms and CN risk in a codominant model. However, using a recessive model, an association between the PstI polymorphism and CN risk was observed (odds ratio: 2.10, 95% confidence interval: 0.96-4.62, P = 0.06), indicating that individuals with the homozygous rare genotype have a higher risk of developing CN compared to those with homozygous wild-type and heterozygous genotypes. When stratified by ethnicity, the PstI polymorphism was significantly correlated with CN susceptibility in non-Asians (odds ratio: 3.74, 95% confidence interval: 1.13-12.43, P = 0.03). This meta-analysis suggests that the CYP2E1 PstI polymorphism increases the risk of CN in non-Asians.

Abstract 3252: A regulatory variant in CYP2E1 affects the risk of lung squamous cell carcinoma

Abstract Background: Cytochrome P450 2E1 (CYP2E1), an ethanol-inducible enzyme, has been shown to metabolically activate various carcinogens, which is critical for the development of cancers. It has demonstrated that CYP2E1 polymorphisms alter the transcriptional activity of the gene. However, studies on the association between CYP2E1 PstI polymorphism and non-small cell lung cancer have reported conflicting results. Thus, the gain of the present study was to investigate whether CYP2E1 PstI polymorphism is associated with the development of non-small cell lung cancer in Chinese population. Method: A case-control study was conducted in which CYP2E1 PstI polymorphism was analyzed in 526 Chinese patients with non-small cell lung cancer and 526 age-matched healthy controls by PCR-RFLP. Odds ratios were estimated by multivariate logistic regression. Result: For CYP2E1 PstI polymorphism, C allele carriers (OR=0.67; CI=0.51-0.87; P=0.002) was associated with a decreased risk of non-small cell lung cancer when compared with GG homozygotes. In the group analyses by pathological types, for lung SCC and other types the ORs of the C allele carriers were (OR=0.60; CI=0.41-0.88; P=0.009) and (OR=0.54; CI=0.30-0.99; P=0.045), respectively. In the group analyses by smoking status, there was a significant association among nonsmokers (OR=0.57; CI=0.40-0.81; P=0.002), but not smokers. In the group analyses by TNM stage, there was no significance between CYP2E1 PstI polymorphism and the grade of non-small cell lung cancer. Conclusion: CYP2E1 PstI polymorphism is associated with decreased risk of development of non-small cell lung cancer and lung SCC or other types in Chinese patients. Key Words: lung cancer; CYP2E1; gene polymorphism; susceptibility; genetic variant Citation Format: Lei Cao, Jia Lin, Bing He, Hongge Wang, Juan Rao, Yingwen Liu, Xuemei Zhang. A regulatory variant in CYP2E1 affects the risk of lung squamous cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3252. doi:10.1158/1538-7445.AM2014-3252

Significant genotype difference in the CYP2E1 PstI polymorphism of indigenous groups in Sabah, Malaysia with Asian and non-Asian populations.

CYP2E1 PstI polymorphism G-1259C (rs3813867) genotype distributions vary significantly among different populations and are associated with both diseases, like cancer, and adverse drug effects. To date, there have been limited genotype distributions and allele frequencies of this polymorphism reported in the three major indigenous ethnic groups (KadazanDusun, Bajau, and Rungus) in Sabah, also known as North Borneo. The aim of this study was to investigate the genotype distributions and allele frequencies of the CYP2E1 PstI polymorphism G-1259C in these three major indigenous peoples in Sabah. A total of 640 healthy individuals from the three dominant indigenous groups were recruited for this study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) at G-1259C polymorphic site of CYP2E1 gene was performed using the Pst I restriction enzyme. Fragments were analyzed using agarose gel electrophoresis and confirmed by direct sequencing. Overall, the allele frequencies were 90.3% for c1 allele and 9.7% for c2 allele. The genotype frequencies for c1/c1, c1/c2 and c2/c2 were observed as 80.9%, 18.8%, and 0.3%, respectively. A highly statistical significant difference (p<0.001) was observed in the genotype distributions between indigenous groups in Sabah with all Asian and non-Asian populations. However, among these three indigenous groups, there was no statistical significant difference (p>0.001) in their genotype distributions. The three major indigenous ethnic groups in Sabah show unique genotype distributions when compared with other populations. This finding indicates the importance of establishing the genotype distributions of CYP2E1 PstI polymorphism in the indigenous populations.

Functional RsaI/PstI polymorphism in cytochrome P450 2E1 contributes to bladder cancer susceptibility: evidence from a meta-analysis.

Cytochrome P450 2E1 (CYP2E1) might be involved in the development of bladder cancer. However, previous studies of any association between CYP2E1 RsaI/PstI polymorphism and bladder cancer risk have yielded conflicting results. In this study, we performed a more precise estimation of the relationship by a meta-analysis based on the currently available evidence from the literature. To assess the effect of CYP2E1 RsaI/PstI polymorphism on bladder cancer susceptibility, a meta-analysis of 6 available studies with 1,510 cases and 1,560 controls were performed through Feb 2014. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to estimate the strength of association for CYP2E1 RsaI/PstI polymorphism under different genetic models. When available studies were pooled into the meta-analysis, we found that the C1C2 and C2C2 genotypes of CYP2E1 RsaI/PstI polymorphism significantly decreased bladder cancer risk under different genetic models (heterozygote: OR=0.766, 95%CI=0.613-0.957, POR=0.019; homozygote: OR=0.51, 95%CI=0.303- 0.858, POR=0.011; dominant: OR=0.733, 95%CI=0.593-0.905, POR=0.004; recessive: OR=0.565, 95%CI=0.337-0.947, POR=0.030). Subgroup analysis indicated that C2C2 genotype was significantly associated with decreased bladder cancer risk under the homozygote genetic model in Caucasians. There was no evidence of heterogeneity or publication bias. The current meta-analysis suggested that the CYP2E1 RsaI/ PstI polymorphism might be associated with bladder cancer susceptibility, especially in Caucasians. Further studies are needed to validate the above conclusion.

P0194 Association between abdominal obesity and type 2 diabetes and HSP70-2 (+1267) gene mutation in colorectal cancer

<h3>Background</h3> The number of patients with colorectal cancer (CRC) is increasing, as is mortality for patients with CRC. Previous reports have shown that heat-shock protein 70-2 (+1267) may be associated with CRC. However, genetic analysis has not been done for effect of the <i>HSP70-2</i> (+1267) gene in association with obesity and type 2 diabetes in CRC. The aim of this study is to investigate whether <i>HSP70–2</i> (+1267) gene polymorphism is involved in susceptibility to CRC in Iranian patients with obesity and type 2 diabetes and whether it correlates with CRC progression in these patients. <h3>Methods</h3> 50 genetically unrelated patients with CRC and 50 healthy controls were typed for the <i>HSP70-2</i> (+1267) PstI polymorphism with use of restriction fragment length polymorphism (RFLP) analysis (alleles A and B). Patients with CRC were classified into two types: those with obesity and type 2 diabetes and those without obesity and type 2 diabetes. <h3>Findings</h3> Our RFLP PCR analysis and polymorphism analysis revealed that <i>HSP70</i>-<i>2</i> has three type of allele, and that the BB allele (1267 A/G) was significantly more common in patients with obesity and type 2 diabetes than in those in the control group (<i>p</i>=0.0001). <h3>Interpretation</h3> Our data suggest that the BB allele of <i>HSP70-2</i> (+1267 A/G) in CRC patients is associated with hereditary obesity, and in lower efficiency, with type 2 diabetes.

Polymorphism of heat shock protein 70-2 and enterocutaneous fistula in Chinese population.

To investigate whether the heat shock protein 70-2 (HSP70-2) polymorphism is associated with enterocutaneous fistulas in a Chinese population. This study included 131 patients with enterocutaneous/enteroatmospheric fistulas. Patients with inflammatory bowel disease or other autoimmune diseases were excluded from this study. All patients with enterocutaneous/enteroatmospheric fistulas were followed up for three months to observe disease recurrence. In addition, a total of 140 healthy controls were also recruited from the Jinling Hospital, matched according to the sex and age of the patient population. Genomic DNA was extracted from peripheral blood from each participant. The HSP70-2 restriction fragment length polymorphism related to the polymorphic PstI site at position 1267 was characterized by polymerase chain reaction (PCR). First PCR amplification was carried out, and then PCR products were digested with PstI restriction enzyme. The DNA lacking the polymorphic PstI site within HSP70-2 generates a product of 1117 bp in size (allele A), whereas the HSP70-2 PstI polymorphism produces two fragments of 936 bp and 181 bp in size (allele B). The frequency of the HSP70-2 PstI polymorphism did not differ between patients and controls; however, the A allele was more predominant in patients with enterocutaneous fistulas than in controls (60.7% vs 51.4%, P = 0.038, OR = 1.425, 95%CI: 1.019-1.994). Sixty-one patients were cured by a definitive operation, drainage operation, or percutaneous drainage while 52 patients were cured by nonsurgical treatment. There was no significant difference in the frequency of the HSP70-2 PstI polymorphism between the patients who had surgery compared to those who did not (P = 0.437, OR = 1.237, 95%CI: 0.723-2.117). Moreover, 11 patients refused any treatment for economic reasons or tumor burden, and 7 patients with enterocutaneous fistulas (5.8%) died during the follow-up period. However, there was no significant difference in the frequency of the HSP70-2 PstI polymorphism between the patients who survived compared to those who died (P = 0.403, OR = 0.604, 95%CI: 0.184-1.986). The A allele of the HSP70-2 PstI polymorphism was associated with enterocutaneous fistulas in this Chinese population.

Crohn's disease and polymorphism of heat shock protein gene HSP70‐2 in the Chinese population

Crohn's disease (CD) is a multifactorial disorder with a pivotal role of the genetic component. A single nucleotide polymorphism in heat shock protein 70-2 (HSP70-2) has been shown to be associated with a severe clinical course in CD. The purpose of this study was to identify associations between the HSP70-2 polymorphism and the clinical courses of CD in the Chinese population. One hundred patients with CD and 190 healthy individuals were genotyped for the HSP70-2 PstI polymorphism by restriction fragment length polymorphism analysis. The genotype frequency of the PstI polymorphism did not differ between patients and controls. The A allele was higher in CD patients than in controls (61% vs 52%, P = 0.047, odds ratio [OR] = 1.423, 95% confidence interval [CI]: 1.004-2.015). Furthermore, this polymorphism was higher in the penetrating or fistula surgery of CD patients than in controls (63% vs 52%, P = 0.049, OR = 1.530, 95% CI: 1.001-2.337; Table ). But there was no significant difference between the penetrating or fistula surgery patients and no surgery patients (P = 0.673, OR = 0.883, 95% CI: 0.495-1.574). We used multivariate analysis to determine the effects of genotypes on sex, disease behavior, disease location, and so on. No significant difference was observed between these parameters and genotype. This study reported that the allele A of PstI polymorphism was the association between CD and HSP70-2 gene in the Chinese population. It was also association between penetrating or fistula surgery of CD and HSP70-2 gene in the Chinese population.

Hsp70-2 gene polymorphism: susceptibility implication in Tunisian patients with coronary artery disease

Coronary artery disease (CAD) is a multifactorial disease where genetic and environmental factors interact in complex ways to cause the disease. Heat shock protein genes are involved in the progress of CAD. This implies that genetic variants of Hsp70–2 genes might contribute to the development of the CAD.Aim of studyThe aim of this study was to characterize statistical correlation of linkage between lipid profiles, polymorphism PstI site of Hsp70–2 gene and CAD.Patients and methodsThis study was carried out on Tunisian patients with CAD recruited from Hospital of Fattouma Bourguiba of Monastir-Tunisia. Polymerase chain reaction and restriction enzymes were used to determine the genotypic distributions in 252 unrelated patients and 151 healthy control subjects. Further, ApoA-I and ApoB as well as the serum total of cholesterol, HDL, triglyceride, and hs-CRP levels were measured.ResultsWe showed a decreased level of ApoA-I, whereas the levels of each of ApoB and hs-CRP were increased in patients with CAD compared with control group. In addition our studies of a polymorphic PstI site of Hsp70-2 gene at position 1267 of the Hsp70–2 gene have revealed that the allelic frequency of P2 was significantly more frequent in CAD patients than controls group (p=0.007, OR=1.495). The genotypic distribution showed a high incidence of P2/P2 genotype in CAD patients (0.190) compared to healthy control (0.009) with reach significant difference (p=0.006). The P2 carriers showed a significantly increased of Total-Cholesterol (CT) and C-reactive protein (hs-CRP) levels in CAD patients (p=0.008 and p=0.018, respectively).ConclusionThe high incidence of P2-Hsp70-2 genotype in CAD patients and the significantly association of P2/P2 genotype with elevated Total Cholesterol and hs-CRP levels, supported that P2–Hsp70–2 genotype has susceptibility implication in CAD and could increased the risk of CAD in Tunisian population.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1118340895703689

The Role of Bactericidal/Permeability-Increasing Protein in Men with Chronic Obstructive Pulmonary Disease

Background and objective: Bactericidal/permeability-increasing protein (BPI) is a member of the pattern recognition receptors of the innate immune system. Recently, an association between genetic polymorphism in the BPI gene and a risk of airflow decline after transplantation was demonstrated, but whether these findings are reproducible in nontransplantation populations, such as those with COPD, is still unknown. The aim of this study is to explore the role of BPI in COPD. Methods: The genotypes of 107 patients with COPD and 110 control subjects were evaluated by polymerase chain reaction and polymorphism analysis of the BPI genes and ELISA analysis of the plasma BPI level. All subjects were men over 40 years old who smoked. Results: BPI mutation PstI (T→C) polymorphism in intron 5 was associated with an increased risk of developing COPD (OR 3.73, 95%CI: 1.62–9.10), and the frequency was significantly increased in the COPD group compared with the control group (26/107 [24.3%] vs 12/110 [10.9%], p = 0.002). In addition, COPD patients exhibited a decreased plasma level of BPI compared with the control group (10.6 ± 2.2 vs 23.4 ± 2.1ng/ml, p < 0.0001). Conclusions: BPI mutation (PstI in intron 5) and a decreased plasma BPI level were significant risk factors in susceptibility to COPD. These results demonstrate that BPI genetic mutation and impaired BPI production or release may result in airflow obstruction in smokers.

Null genetic risk of ACE gene polymorphisms with nephropathy in type 1 diabetes among Egyptian population

Reported to date, strong evidence exists in multiple studies for genetic predisposing in the development of diabetic nephropathy, and no studies addressed this issue among Egyptian population. The results of angiotensin converting enzyme gene (ACE) in the susceptibility to nephropathy in type 1 diabetes with nephropathy are conflicting. We aim to identify the associations of two ACE gene polymorphisms ( PstI, A > G substitution and a 287-bp insertion/deletion) with nephropathy in type 1 diabetes in Egyptian children/adolescents. Our case-control study contained 140 diabetic individuals; 80 diabetic with nephropathy as cases, and 60 diabetic subjects without nephropathy as control group. Amplified DNA from peripheral leucocytes/buccal mucosa was genotyped for using polymerase chain reaction and enzymatic assay. We found no significant differences in the distribution of ACE insertion/deletion and PstI genotypes or allele frequencies were observed between the examined groups. Frequencies of PstI–indel haplotypes were similar in all of our study groups. In both cases and control subjects, ACE activity and microalbuminuria were highest among D/D homozygotes and lowest in I/I homozygotes, while a dissimilar result was seen in PstI polymorphism. Our findings in Egyptian population strongly conclude that there is no association between the ACE gene I/D and PstI polymorphisms with nephropathy in type 1 diabetes.

Common Variants ofHMGCR, CETP, APOAI, ABCB1, CYP3A4, andCYP7A1Genes as Predictors of Lipid-Lowering Response to Atorvastatin Therapy

There is interindividual variation in lipid-lowering response to statins. The objective of this study was to investigate whether common variation in genes involved in lipid and statin metabolism modify the effect of statins on serum total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol concentration in coronary artery disease (CAD) patients. We studied the association between 18 single-nucleotide polymorphisms (SNPs) in six genes (HMGCR, CETP, APOAI, ABCB1, CYP3A4, CYP7A1) in response to atorvastatin therapy (20 mg/day) in 265 newly diagnosed CAD patients using multivariable adjusted general linear regression. Variant alleles of ABCB1 (-41A/G), HMGCR SNP29 G/T, rs5908A/G, rs12916C/T, and CYP7A1-204A/C polymorphisms were significantly associated with attenuated LDL-C reduction and variant alleles of CETP TaqI, -629C/A, and APOAI PstI polymorphisms were associated with higher increase in high-density lipoprotein-cholesterol. A three-loci interaction model consisting of CYP7A1rs892871AA/APOAIPstIP1P1/HMGCR rs12916CT was a better predictor for LDL-C lowering, when compared with single polymorphisms analysis on statin response. Variant genotypes of APOAI -2500C/T, CETP 405I/V, and ABCB1 3435C/T showed higher risk of myocardial infarction events (p < 0.05) in a 1-year follow-up of CAD patients. These results suggest that SNPs in lipid and statin pathway genes are associated with reduced LDL-C lowering by statins and identify individuals who may be resistant to maximal LDL-C lowering by statins.

Polymorphisms in Alcohol Metabolizing Genes and the Risk of Head and Neck Cancer in a Brazilian Population

The incidence of head and neck cancer (HNC) in Brazil has increased substantially in recent years. This increase is likely to be strongly associated with alcohol and tobacco consumption, but genetic susceptibility also should be investigated in this population. The aim of this study was to evaluate the association of polymorphisms in genes of alcohol metabolism enzymes and the risk of HNC. A hospital-based case-control study was conducted in São Paulo, Brazil. We here investigated ADH1C Ile(350)Val, ADH1B Arg(48)His, ADH1B Arg(370)Cys and CYP2E1*5A PstI polymorphisms by PCR-RFLP Polymerase Chain Reaction - Restriction Fragment Length Polymorphism in 207 histopathologically confirmed HNC cases (184 males and 23 females) and 244 cancer-free controls (225 males and 19 females) admitted as in-patients in the same hospital. Chronic alcohol intake increased approximately four times the risk of HNC. The mutant genotype ADH1B Arg(48)His was more frequent in controls (12.7%) than HNC patients (5.8%) conferring protection for the disease (odds ratio (OR) = 0.42; 95% confidence interval (CI ), 0.21-0.85). Similar results were observed for individuals with ADH1B*2 (OR = 0.41; 95% CI , 0.20-0.82) or ADH1B*2/ADH1C*1 (OR = 0.32; 95% CI , 0.13-0.79) mutated haplotypes. Multiple regression analyses showed that individuals with the mutant genotype ADH1B Arg(48)His who consume alcohol >30 g/L/day have more than four times the risk for HNC (OR = 4.42; 95% CI, 1.21-16.11). The fast alcohol metabolizing genotypes may prevent HNC when the amount of alcohol intake is <30.655 g/L/day.

Influence of socioeconomic lifestyle factors and genetic polymorphism on type 2 diabetes occurrences among Tunisian Arab and Berber groups of Djerba Island

Type 2 diabetes mellitus (T2DM) is characterized by three major metabolic abnormalities: impaired insulin-stimulated glucose uptake in muscle and adipose tissues, alterations in glucose-stimulated insulin secretion, and increased hepatic glucose production. Both genetic and environmental factors contribute to its development. The insulin gene (INS), insulin receptor gene (INSR), and insulin receptor substrate 1 gene (IRS1), identified by polymerase chain reaction and digestion with selected restriction enzymes PstI, NsiI, and BstnI, have been proposed as T2DM candidate genes. To determine the contribution of genetic and environmental factors on the occurrence of T2DM, we examined the frequency of T2DM among two ethnically diverse populations, Arabs and Berbers, who have shared the same environment, the island of Djerba, for thousands of years. Both populations have a high prevalence of obesity,T2DM, and a high consanguinity rate. A total of 162 T2DM men and women were matched to 110 healthy male and female controls. Results showed that the NsiI polymorphism in INSR and BstnI polymorphism of IRS1 were significantly associated with T2DM only among the Berber group. The PstI polymorphism in INS, was not associated with T2DM in either group. Sedentary lifestyles, lower physical activity, and lower educational levels were associated with T2DM among the Berber group. These findings suggest that the insulin receptor gene and lifestyle factors in combination may contribute to the occurrence of T2DM in the Berber portion of this island population.

A PstI polymorphism at 3′UTR of goat POU1F1 gene and its effect on cashmere production

POU1F1 is a positive regulator for prolactin (PRL) whose metabolites may directly or indirectly affect some aspects of the hair growth cycle, therefore, POU1F1 gene is an important candidate gene for cashmere traits selection through marker-assisted selection (MAS). Hence, in this study, the PCR-RFLP method was applied to detect a T>C transition determining a PstI polymorphism at the 3'UTR of POU1F1 locus and evaluate its associations with cashmere traits in 847 Inner Mongolia White Cashmere goats. In the analyzed population, the allelic frequencies for the T and C alleles are 0.959 and 0.041, respectively and the genotypic frequencies are in Hardy-Weinberg equilibrium (P > 0.05). Moreover, significant statistical relationships between the PstI polymorphism of POU1F1 gene and goat cashmere yields were found (*P < 0.05). When compared with TC genotype, TT genotype was associated with superior cashmere yields in 2, 4, and 5 years old individuals, as well as with average cashmere yield. Hence, TT genotype is suggested to be a molecular marker for senior cashmere yield.

Investigation of QTL regions on Chromosome 17 for genes associated with meat color in the pig

Previous studies have uncovered several significant quantitative trait loci (QTL) relevant to meat colour traits mapped at the end of SSC17 in the pig. Furthermore, results released from the porcine genome sequencing project have identified genes underlying the entire QTL regions and can further contribute to mining the region for likely causative genes. Ten protein coding genes or novel transcripts located within the QTL regions were screened for single nucleotide polymorphisms (SNPs). Linkage mapping and association studies were carried out in the ISU Berkshire x Yorkshire (B x Y) pig resource family. The total length of the new SSC17 linkage map was 126.6 cM and additional markers including endothelin 3 (EDN3) and phosphatase and actin regulator 3 (PHACTR3) genes were assigned at positions 119.4 cM and 122.9 cM, respectively. A new QTL peak was noted at approximately 120 cM, close to the EDN3 gene, and for some colour traits QTL exceeded the 5% chromosome-wise significance threshold. The association analyses in the B x Y family showed that the EDN3 BslI and PHACTR3 PstI polymorphisms were strongly associated with the subjective colour score and objective colour reflectance measures in the loin, as well as average drip loss percentage and pH value. The RNPC1 DpnII and CTCFL HpyCH4III polymorphisms were associated with some meat colour traits. No significant association between CBLN4, TFAP2C, and four novel transcripts and meat colour traits were detected. The association analyses conducted in one commercial pig line found that both EDN3 BslI and PHACTR3 PstI polymorphisms were associated with meat colour reflectance traits such as centre loin hue angle and Minolta Lightness score. The present findings suggested that the EDN3 and PHACTR3 genes might have potential effects on meat colour in pigs, and molecular mechanisms of their functions are worth exploring.

Genotypes of varicella‐zoster virus wild‐type strains in Germany

Surveillance of varicella-zoster virus (VZV) genotypes is indicated in Germany after implementation of universal varicella vaccination. This article reports genotyping data of 77 VZV strains obtained from 54 patients with varicella, 1 newborn with congenital varicella syndrome, 2 fetuses with intrauterine VZV infection and 20 cases with zoster. Fragments of the open reading frames (ORF) 1, 21, 22, 37, 50, 54, and 60 were analyzed by sequencing. In addition, the PstI polymorphism of the ORF 38 was characterized. Thirty strains, 22 from varicella and 8 from zoster, had the genetic markers of genotype E2, 2 of them carried new single nucleotide polymorphisms (SNP). Twenty-nine VZV isolates, 17 from varicella, and 12 from zoster, could be analyzed as E1 strains, 6 of them as E1 variants containing individual SNPs. Finally, 17 strains taken from primary VZV infection were classified as genotype M1, 13 of which belonged to the M1 subtype 1, 3 to the M1 subtype 2, and 1 to the M1 subtype 3. One strain was regarded as potential E2/J recombinant. In conclusion, VZV genotypes E2, E1, and M1 can be found in nearly equal incidence in varicella in Germany. The most frequent group is attributed to the genotype E2. Genotype M1 strains can only be detected after primary VZV infection and not in zoster cases. The possible recombinant could not be classified definitely by the scattered SNP method used and, therefore, has to be confirmed by full-genome sequencing studies.