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PubMed2025

A Complete Picture of the CYP2D6 Heterogeneity in Northeastern Italian Genetic Isolates.

The CYP2D6 gene is a highly polymorphic pharmacogene involved in the metabolism of 25% of commonly used drugs. We aim to assess the feasibility of extracting relevant pharmacogenomic information from Whole Genome Sequencing (WGS) data and to highlight any difference in CYP2D6 allele frequencies between the northeastern Italian and European populations. To achieve this aim, WGS was performed on two cohorts: 664 individuals from six different isolated communities (FIC) and 123 outbred Italian individuals (FOP). In silico CYP2D6 genotyping was performed and allele frequencies from the FIC cohort were compared to those of FOP and European individuals from 1000 Genomes. Interestingly, 18 alleles identified in FIC were absent in the control cohorts. In particular, 13 individuals carried the extremely rare CYP2D6*28x2 allele, whose activity is unknown. Moreover, we identified a carrier of the CYP2D6*34x2 allele, which has never been described before. The population structure and genetic differentiation of the cohorts were investigated, revealing that the genetic isolates differ only slightly from the outbred and the European populations, but still offer new insight into CYP2D6 heterogeneity. The findings described here will be relevant to tailoring the treatments in the northeastern Italian population.

Cytochrome P-450 CYP2D6↗
PubMed2003

Linkage analysis of the candidate genes of familial restless legs syndrome.

This research was performed to investigate the relationship between 16 candidate genes responsible for dopaminergic transmission or iron metabolism and familial restless legs syndrome. Genotyping was performed in a Han restless legs syndrome family using the technique of fluorescence-based genescan with the microsatellite markers selected in chromosomal regions flanking the candidate genes. Classical linkage analysis was conducted under the autosomal dominant genetic mode. Results showed that all of the LOD scores at recombination fraction 0.00 are smaller than -2.00, which indicated that these loci were not linked to familial restless legs syndrome. No linkage was found between the candidate genes and RLS in this family. Familial restless legs syndrome may be caused by another gene related to dopaminergic transmission and iron metabolism or there is new mechanism involved in this disease.

Adolescent↗
PubMed2003

Genotypic analysis of primary and metastatic cutaneous melanoma.

Microdissection genotyping was performed on 16 cases of melanoma, including two cutaneous and one lymph node metastases. Three benign nevi were used as controls. Where possible, tumor was microdissected at several sites. Genotyping involved assessment of loss of heterozygosity [LOH]), which was accomplished using a panel of nine polymorphic tetranucleotide microsatellites. Polymerase chain reaction was performed on the normal tissue sample to establish microsatellite heterozygous status. Informative markers were then tested on microdissected lesional tissue and scored for the presence and extent of allelic imbalance (AI). Microsatellite informativeness varied from 33% to 66%. Benign nevi were without AI. All invasive melanomas manifested acquired allelic loss, which involved 75% or 100% of the markers shown to be informative for each subject. Eleven of 13 (84%) primary melanomas demonstrated intratumoral heterogeneity of AI consistent with development of tumor subclones with differing genotypic profiles within thin as well as thick melanomas. Although a consistent pattern did not emerge among the markers, LOH of 9p21 (D9S254) occurred in 60% (9/15) of the cases followed by 40% of cases displaying LOH of 1p34, p53, 10q (MXI1), and 10q23 (D10S520) and 25% with 5q21 (D5S 592) abnormalities. A third of the cases including the metastatic foci demonstrated two different patterns of AI affecting alternative alleles of the same genomic marker within different parts of the melanoma. Two melanomas in situ did not display LOH of any markers in the informative cases although the in situ component in the invasive tumors had allelic losses that were in part similar to the invasive areas. The results of this study support the expanded use of microdissection genotyping and explore other markers to define the unique mutational profile for malignant melanoma that may complement other histologic characteristics of melanoma.

Alleles↗
PubMed2002

Stromelysin 1 (matrix metalloproteinase 3) and HLA-DRB1 gene polymorphisms: Association with severity and progression of rheumatoid arthritis in a prospective study.

OBJECTIVE: To test the hypothesis of an association between a polymorphism in the matrix metalloproteinase 3 (MMP-3) gene promoter and the susceptibility, severity, and progression of rheumatoid arthritis (RA), and to further document the association between HLA-DRB1 alleles encoding the shared epitope (SE) and the severity and progression of RA. METHODS: Patients with early RA (n = 103) were included in this prospective study. A total radiographic damage score (TDS; by the Sharp/van der Heijde method) was used to quantify RA severity at baseline and after 4 years of followup. The 5A/6A biallelic polymorphism in the MMP-3 gene promoter was analyzed using fluorescence-based polymerase chain reaction (PCR). HLA-DRB1 genotyping was performed using PCR methods. Control subjects (n = 127) were unrelated healthy individuals. RESULTS: MMP-3 allele carriage rates and allele and genotype frequencies did not differ between patients and controls. The MMP-3 6A/6A genotype was associated with the highest TDS both at baseline and after a 4-year followup and with the highest progression of the TDS over the 4 years of followup. The DRB1 SE+/+ genotype was associated with the highest TDS after a 4-year followup and with the highest progression of the TDS over the 4 years of followup. Patients homozygous for MMP-3 6A and DRB1 SE had the highest progression of the TDS. CONCLUSION: This study provides the first evidence of an association between a polymorphism in the MMP-3 gene promoter and the severity and progression of RA, but not RA susceptibility. Investigation of this polymorphism could be combined with that of DRB1 gene polymorphism to improve the predictive accuracy and management strategy in early RA.

Alleles↗
PubMed2001

Association between total serum calcium and the A986S polymorphism of the calcium-sensing receptor gene.

Serum calcium is under tight physiological control, but it is also a quantitative trait with substantial genetic regulation. Mutations of the CASR gene cause familial hypocalciuric hypercalcemia or autosomal dominant hypoparathyroidism, depending on whether they decrease or increase, respectively, ligand binding to the receptor protein. We described an association between ionized calcium and a common polymorphism (A986S) found in the cytoplasmic tail of this G protein-coupled receptor. We report here on an independent study of 387 healthy young women. Genotyping was performed by allele-specific amplification and serum chemistries were measured by automated clinical assay. Frequencies of SS, AS, and AA genotypes were 6, 107, and 274, respectively, yielding a 986S allele frequency of 15.4%. Mean total serum calcium (Ca(T)) was significantly higher in the SS (9.88 +/- 0.29 mg/dL, P = 0.015) and AS groups (9.45 +/- 0.05 mg/dL, P = 0.002), than in the AA group (9.23 +/- 0.04 mg/dL). In multiple regression modeling, the A986S genotype remained an independently significant predictor of Ca(T) (P < 0.0001) when serum albumin, globulin, inorganic phosphate, and creatinine covariates were included. These data are the first to show significant association between a common polymorphism and concentrations of a serum electrolyte. The A986S polymorphism is also a potential predisposing factor in disorders of bone and mineral metabolism.

Adolescent↗
PubMed1999

Response to interferon alfa-2b therapy in mutitransfused children with beta-thalassemia and chronic hepatitis C.

Hepatitis C virus is responsible for the majority of cases of post-transfusion non-A non-B hepatitis in patients with thalassemia major. Interferon alfa is an effective treatment for patients with chronic hepatitis C. Response to therapy is related to the duration of treatment, the viral load in serum, and the hepatitis C virus genotype. The purpose of this study was to estimate the response of multitransfused children with beta-thalassemia and chronic hepatitis C to interferon alfa-2b therapy. Thirteen patients with beta-thalassemia and chronic hepatitis C, (mean age+/-SD, 14.1 +/- 1.7 years) participated in the study. Liver biopsy, estimation of HCV RNA, and virus genotyping were performed before onset of treatment. All patients were positive for HCV RNA in a low concentration; two patients carried the la genotype, four had genotype 3, and seven had genotype 4. Patients were treated with 3 x 10(6) U of subcutaneous interferon alfa-2b three times weekly. Eleven of 13 patients received therapy for 18 months; the remaining two underwent therapy for 6 months. Six of 13 patients responded completely to therapy, four responded partially, and three did not respond at all. The grade of inflammation and stage of fibrosis was lower in complete responders. Complete responders had lower ferritin values compared with the values for partial and nonresponders before starting therapy. The results suggest that interferon therapy should be recommended for children with beta-thalassemia major complicated by a low viral concentration of hepatitis C.

Adolescent↗
PubMed2006

Platelet glycoprotein polymorphisms: risk, in vivo expression and severity of atherothrombotic stroke in Chinese.

BACKGROUND: Polymorphisms in platelet glycoprotein (GP) receptors Ia, Ib and IIIa may be heritable risk factors for platelet-dependent thrombosis leading to death. The precipitation of stroke by occlusive thrombi has led to the investigation of the platelet surface GP receptors, that are involved in critical steps in the activation of platelets. Three polymorphisms in the GP Iba gene and one in each of GPIIIa, GP Ia were selected based on the evidence of functional effects on structure or expression as candidates for risk. We also determined whether these polymorphisms were associated with in vivo expression levels of platelet GP receptors and the severity of the neurological deficit. METHODS: A Chinese hospital-based case-control study was conducted with 119 cases of atherothrombotic stroke and 166 age and sex matched controls. Genotyping was performed on lymphocyte DNA by standard methods and platelet GP expression levels were measured by flow-cytometry. RESULTS: Allele and genotype frequencies of the GP receptor polymorphisms differ considerably between ethnic populations. We found the D allele of the GP Iba VNTR polymorphism was significantly associated with atherothrombotic stroke in our Chinese cohort, however we did not find a relationship among these polymorphisms, the expression levels of GP receptors and severity of the neurological deficit. CONCLUSIONS: In our Chinese cohort the D allele of the GP Iba VNTR polymorphism is associated with atherothrombotic stroke. The number of VNTR repeats alters the length of amino acid sequence, which might affect the structure and function of this receptor.

Adult↗
PubMed2005

CTLA-4 gene 49A/G polymorphism in Turkish patients with Behçet's disease.

Genetic factors predisposing individuals to Behçet's disease (BD) are considered to play important roles in the development of the disease. Patients with BD exhibit elevated levels of pro-inflammatory cytokines, and affected organs show a significant neutrophil and lymphocyte infiltration. Current evidence suggests that the activated lymphocytes contribute to neutrophil and endothelial cell activation in these patients. The cytotoxic T lymphocyte-associated antigen (CTLA)-4 molecule plays an important role in immune regulation by downregulating T-cell activation, and the CTLA-4 49A/G polymorphism in the exon 1 has been shown to be associated with a number of autoimmune diseases. In an attempt to demonstrate whether there is an association of the CTLA-4 49A/G polymorphism with BD in the Turkish population, we genotyped 59 Turkish patients and 99 healthy individuals for single-nucleotide polymorphisms. For this purpose, genomic DNA was obtained from the peripheral blood of individuals and the region of interest was amplified using PCR. Genotyping was performed using the BbvI restriction endonuclease. It was shown that the distribution of the CTLA-4 exon 1 49A/G allele and genotype frequencies did not differ between patients with BD and healthy controls. However, allele and genotype frequencies of CTLA-4 49 A and A/A were significantly higher in patients with ocular involvement compared with patients without these symptoms (90.6% vs. 65.1%, odds ratio (OR) = 9.67, P = 0.011; and 81.25% vs. 39.5%, OR = 9.56, P = 0.015, respectively). A statistically significant difference in the A allele frequency was observed in patients with erythema nodosum-like lesions (86.1% vs. 65.8%, OR = 6.24, P = 0.04). There was also an increase in A/A genotype frequency, but the difference was not statistically significant (72.2% vs. 41.5%, OR = 6.5, P = 0.068). Our data suggest that BD patients with ocular involvement and erythema nodosum-like lesions have a higher frequency of both the A allele and the A/A genotype at position 49 of exon 1 of CTLA-4. These results may also indicate that CTLA-4 is a disease-modifying rather than a susceptibility gene for BD.

Adult↗
PubMed2003

Factor V Leiden polymorphism and the rate of fibrosis development in chronic hepatitis C virus infection.

BACKGROUND: The rate of progression to cirrhosis varies among individuals chronically infected with the hepatitis C virus (HCV). Coagulation pathway activation in models of hepatic fibrosis suggests variation in coagulation pathway components may influence the rate of fibrosis. We hypothesised that polymorphisms of the coagulation factors II and V affect the rate of progression to cirrhosis in HCV infected subjects. METHODS: We studied the relationship between rate of fibrosis (calculated by dividing the fibrosis stage by duration of infection) and genotypes of specific coagulation pathway genes in 352 White European patients infected with HCV. Genotyping was performed using reverse line blot hybridisation. RESULTS: The rate of fibrosis was significantly higher in patients with the factor V Leiden genotype (Arg560Gln) (ANOVA, p=0.004). In disease association studies, a significant association was seen (Fisher's exact test, p=0.029; odds ratio 3.28 for fast progression to cirrhosis (expected to reach cirrhosis in less than 30 years) if heterozygous for factor V Leiden). No associations were seen between factor II genotype and fibrosis rate. CONCLUSIONS: Possession of the factor V Leiden polymorphism significantly increases the risk of rapid disease progression in HCV, suggesting a role for the coagulation system in the pathogenesis of fibrotic liver disease.

Adult↗
PubMed1999

Angiotensin-converting enzyme gene polymorphism and geometric patterns of hypertensive left ventricular hypertrophy.

Polymorphism in the angiotensin-converting enzyme (ACE) gene has been found to be associated with left ventricular hypertrophy (LVH) in patients with essential hypertension (EHT) in certain populations. We sought to evaluate, in a Japanese population, whether ACE genotype is related to left ventricular mass, or to the geometry of LVH in EHT. Eighty-seven patients with EHT were examined. Their relative wall thickness (RWT) and left ventricular mass index (LVMI), determined by echocardiogram, were used to divide them into 4 groups: normal (normal RWT and LVMI, n = 35); concentric remodeling (increased RWT but normal LVMI, n= 10); eccentric hypertrophy (increased LVMI but normal RWT, n = 20); and concentric hypertrophy (increased LVMI and RWT, n = 22). Genetic analysis for ACE genotypes was performed on peripheral leukocytes using PCR techniques. Interventricular septal thickness and RWT were significantly greater in the patients with the DD genotype than in those with the II genotype, but LVMI did not differ among the three ACE genotypes. The frequency of the DD genotype was higher in the concentric hypertrophy group than in each of the other groups, and the frequency of the II genotype was lower in the concentric hypertrophy group than in either the normal or eccentric hypertrophy group. The geometric pattern of hypertensive LVH was associated with ACE genotype in a Japanese population. The DD genotype may contribute to concentric hypertrophy, but not to eccentric hypertrophy.

Adult↗
PubMed2003

Distribution of interleukin-1beta(+3954) and IL-1alpha(-889) genetic variations in a Thai population group.

BACKGROUND: The severe form of chronic periodontitis (CP) has been reported to be strongly associated with the presence of allele 2 of composite IL-1beta(+3954) and IL-1alpha(-889) genetic polymorphisms (genotype positive). However, other studies have reported conflicting findings, not only on the association between the composite IL-1 gene polymorphisms and CP, but also the link between IL-1 gene polymorphisms and aggressive periodontitis (AgP). These might have resulted from differences in ethnic background and disease entities. The aim of this study was to determine the distribution of IL-1beta(+3954) and IL-1alpha(-889) genetic polymorphisms in a group of Thai subjects based on their periodontal status, including CP, AgP, and healthy groups. METHODS: A total of 123 Thai subjects were clinically and radiographically assessed for their periodontal status. Blood samples were collected by fingerstick and adsorbed onto filter paper. The IL-1beta(+3954) and IL-1alpha(-889) genotypes were performed by polymerase chain reaction, digested with restriction enzymes, and separated by gel electrophoresis. RESULTS: The distribution of allele 1 homozygous genotype was 97.6% and 84.6% for IL-1beta(+3954) and IL-1alpha(-889), respectively. No allele 2 homozygous genotype was detected in either of these two gene loci. Only 1.6% (2 out of 123) of the subjects were genotype positive, which was too low to determine the association between the composite genotype of IL-1beta(+3954) and IL-1alpha(-889) and severe forms of periodontal disease. CONCLUSION: Genetic polymorphism of IL-1 genes in these two loci may not be useful in predicting the severity of periodontal disease in the Thai ethnic group.

Acute Disease↗
PubMed2005

Lack of association between the functional CX3CR1 polymorphism V249I and hepatocellular carcinoma.

Chemokine production by cancer cells constitutes a duality. Leukocyte recruitment under the pressure of chemokines may be beneficial for the host or for the tumor. Recently, the chemokine fractalkine and its receptor CX3CR1 have been shown to be expressed in hepatocytes in vivo and in a human hepatocarcinoma cell line in vitro. Therefore, the aim of this study was to analyze the expression of CX3CR1 in hepatocellular carcinoma (HCC) in vivo and to investigate the prevalence of the genetic CX3CR1 polymorphism V249I in HCC patients since this polymorphism has been associated with reduced number of fractalkine binding sites, reduced cell-cell adhesion and decreased signaling and chemotaxis. Genotyping was performed in 183 patients with histologically proven HCC and 99 healthy controls by RFLP-analysis. The frequency of the individual genotypes was similar in HCC patients and controls. The V249I polymorphism revealed no association with tumor grade and stage, the presence of extrahepatic metastasis or the degree of fibrosis in non-tumorous tissue. In addition to genotyping, CX3CR1 mRNA expression was analyzed by quantitative PCR in 9 HCC specimens and in 6 cases in corresponding non-tumorous liver tissues. CX3CR1 mRNA expression levels in HCC showed high variation between individual patients. Similarly, expression in HCC compared to non-tumorous liver varied, from strong downregulation to remarkable upregulation. CX3CR1 mRNA expression levels showed no correlation to the V249I polymorphism. In summary, these results suggest that the patho-physiological role of individual chemokines in carcinogenesis may vary and that the functional CX3CR1 polymorphism V249I is no genetic risk factor for HCC. However, additional independent studies in HCC patients with different ethnic background will be needed to confirm the present study and to elucidate the functional role of CX3CR1 and its polymorphism V249I in chronic liver disease and hepatocarcinogenesis.

Aged↗
PubMed2003

Left ventricular size, mass and function in relation to angiotensin-converting enzyme gene and angiotensin-II type 1 receptor gene polymorphisms in patients with coronary artery disease.

The objective of the present study was to analyse the potential synergistic influence of the insertion/deletion polymorphism of the angiotensin-converting enzyme gene (I/D ACE) and the A1166C polymorphism of the angiotensin-II type 1 receptor gene polymorphisms (A1166C AT1R) on the left ventricular size and performance. Three hundred sixty and one consecutive, Caucasian patients with angiographically confirmed coronary artery disease (CAD) were enrolled into the study. Left ventricular diameter, mass and function were evaluated by echocardiography. Screening for the I/D ACE and A1166C AT1R genotypes was performed by polymerase chain reaction of genomic DNA, followed by restriction enzyme digestion and agarose gel electrophoresis. The I/D ACE and A1166C AT1R genotypes separately were not significantly associated with the left ventricular size and function parameters in CAD patients. However, trends towards decreased left ventricular ejection fraction (LVEF) as well as increased left ventricular end-diastolic diameter (LVEDD) and left ventricular mass index (LVMI) were observed when patients with genotype DD+CC/AC and DD+CC were compared to patients homozygous only in one locus (DD or CC). Significant increase in LVEDD and LVMI was observed only in patients with a history of anterior myocardial infarction with combined genotype DD+CC/AC or DD+CC. This study does not support the role of the ACE I/D and AT1R A1166C polymorphisms in the determination of the left ventricular size and performance in patients with significant coronary atherosclerosis. However, it indicates that the influence of polymorphisms may be present in specific patient populations.

Angiotensin II↗
PubMed2006

No association between the polymorphisms in matrix metalloproteinase-1 and matrix metalloproteinase-3 promoter regions and colorectal cancer in Chinese.

PURPOSE: Matrix metalloproteinase-1 and matrix metalloproteinase-3 are implicated in all steps of cancer initiation, invasion, and metastasis. Recently, several genetic studies have demonstrated that matrix metalloproteinase-1-1607 ins/delG (1G/2G) polymorphism and matrix metalloproteinase-3-1612 ins/delA (5A/6A) polymorphism modify each transcriptional activity in allele-specific manners. In this study, we investigated whether these functional polymorphisms are associated with colorectal cancer in a Chinese population. METHODS: Matrix metalloproteinase-1 and matrix metalloproteinase-3 genotypings were performed on 126 pathologically diagnosed colorectal cancer patients and 126 age-matched and gender-matched controls by polymerase chain reaction-based denaturing high-performance liquid chromatography analysis or restriction fragment length polymorphism, respectively. RESULTS: The distributions of the matrix metalloproteinase-1 and matrix metalloproteinase-3 genotypes in healthy control subjects were inconsistent with Hardy-Weinberg equilibrium. Neither the genotype frequencies nor allele frequencies of matrix metalloproteinase-1 and matrix metalloproteinase-3 polymorphisms showed significant difference from those in healthy control subjects. There also were no significant associations between matrix metalloproteinase-1 and matrix metalloproteinase-3 genotypes and clinicopathologic features. When we examined the linkage disequilibrium between these two single nucleotide polymorphisms using expectation-maximization algorithm, we found that the two single nucleotide polymorphisms were in a strong linkage disequilibrium, but no significant difference was found in haplotype distribution. CONCLUSIONS: Our present data suggest that the matrix metalloproteinase-1 and matrix metalloproteinase-3 promoter polymorphisms may not be useful markers to predicate susceptibility of colorectal cancer in Chinese.

Case-Control Studies↗
PubMed1998

Genetic variability and diversity for protein and calcium contents in finger millet (Eleusine coracana (L.) Gaertn) in relation to grain color.

Analysis of 36 genotypes of finger millet (Eleusine coracana (L.) Gaertn) with varying seed colors revealed a wide range of protein and calcium contents. White seeded genotypes had higher protein contents, while brown seeded types had a wide range of values. The brown seeded genotype GE 2500 had the highest protein content. Although protein content had significant negative association with calcium content, white seeded types had moderate levels of calcium. The genotypic coefficients of variability were moderate and high for protein and calcium, respectively. High heritability coupled with high genetic advance indicated their governance by additive gene action. A negative significant correlation was observed between protein content and grain yield. Mahalanobis D2 analysis grouped the 36 genotypes into eight clusters. Clustering pattern failed to indicate any relationship between genetic diversity and geographic diversity. Based on genetic diversity and performance, the genotypes MS 1168, MS 174 and CO 13 were found to be suitable for use as parents in a hybridization program for improving yield; the genotypes MS 1168, MS 174 and MS 2869 for protein and Malawi 1915 and CO 11 for calcium. Protein and calcium contents contributed less to genetic divergence.

Calcium↗
PubMed2002

Association of the D8S282 marker near the lipoprotein lipase gene locus with systolic blood pressure in healthy Chinese subjects.

OBJECTIVE: To investigate the association between the marker D8S282 near the lipoprotein lipase (LPL) gene locus, and blood pressure, anthropometric and biochemical parameters in 229 healthy Chinese subjects. METHOD Genotyping was performed using an automated DNA sequencer and the Base ImageIR software. Eight different alleles were identified (272-286 bp) resulting in 15 genotypes in our population. We investigated the association between the common (28.8%) 278 bp allele and the anthropometric and biochemical parameters. RESULTS: In a tertile analysis, the frequency of the 278 bp allele increased linearly ( P = 0.003) with increasing systolic blood pressure (SBP). The relationship was most evident in the females ( n = 141); SBP was higher in homozygotes for the 278 bp allele (117 +/- 10 mmHg, = 12) than those without this allele (109 +/- 9 mmHg, = 77, 0.05) and was gene-dose dependent, and this difference was more significant after adjusting for age (P = 0.004). No relationship between the locus and the anthropometric or biochemical parameters investigated was observed. CONCLUSION: The D8S282 marker near the LPL gene locus contributes to the variance of SBP in healthy Hong Kong Chinese subjects, particularly in females.

Adult↗
PubMed2005

Polymorphism in IGF-2 as a surrogate marker for predisposition towards tobacco chewing-mediated oral cancer.

Insulin and insulin-like growth factors (IGFs) are major determinants of proliferation and apoptosis, thereby playing a significant role in carcinogenesis. Epidemiological evidence associates high levels of INS and IGFs with an increased risk of cancer. Polymorphism of the genes involved in insulin-signaling pathways has been associated with a variable risk for neoplasms in different ethnic and environmental backgrounds. In this study, using PCR-RFLP-based assays, we investigated the distribution of genetic polymorphism in INS and IGF-2 genes in tobacco chewing-mediated oral cancer patients (n = 60) and healthy controls (n = 45) of Indian ethnic origin. The genotyping was performed for +1127 INS-Pst1 in INS and +3580 IGF-2-Msp1 in IGF-2. The frequencies of the IGF-2 genotypes AG, GG and AA found in oral cancer patients were 0.68, 0.2 and 0.12, respectively, whereas in noncancer controls these frequencies were 0.27, 0.71 and 0.02. Frequencies of each allele, i.e. CT, TT and CC of INS gene, were found to be nearly equal in the tumor (0.22, 0.75 and 0.03) as well as the normal (0.27, 0.67 and 0.06) population. A significant difference was observed in genotypic frequencies of IGF-2 and INS in the Indian ethnic population as compared to the Caucasian, African and Hispanic populations. Polymorphism at +1127 INS-Pst1 locus of INS gene does not show an implication in oral cancer, whereas the genotype AG or AA at +3580 IGF-2-Msp1 locus of IGF-2 is associated with progression and increased risk of oral cancer. From our study we can conclude that single nucleotide polymorphisms in the IGF-2 gene can be used as a marker for prediction of the risk of oral carcinogenesis.

Carcinoma, Squamous Cell↗
PubMedDate not supplied

Association of apolipoprotein E genotype with early onset of coronary heart disease in Greek men.

Apolipoprotein (apo) E polymorphism has been associated with coronary heart disease (CHD) although its relation to the age of CHD onset is still not defined. The age of onset of established CHD was obtained from 502 Greek men and compared to 103 healthy men. The age grouping was based on the age of CHD onset (earlier < or =44 years, n = 73, intermediate 45-64 years, n = 321, and later > or =65 years, n = 108). Apo E genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the lipid profile was assessed. No differences in genotype and allele frequencies were found within the CHD groups. The apo epsilon3/4 genotype and the apo epsilon4 allele were less frequent in the earlier-onset group than in healthy men (11.0 % vs 22.3%, Pearson Chi-Square p = 0.028 and 6.8% vs 13.6%, Pearson Chi-Square p = 0.023, respectively). The lipid profile was similar in all genotypes of all groups except for high-density lipoprotein cholesterol levels, which were higher in epsilon2 carriers compared to non-epsilon2 carriers (in mg/dL [+/-SD]; 44 [9] vs 39 [10], in mmol/L [+/-SD]; 1.1 [0.2] vs 1.0 [0.3] p = 0.005). There is an association between apo E genotype and early onset of CHD in Greek men. In the earlier CHD onset group, the apo epsilon3/4 genotype was less frequent compared to healthy men. This supports that the apo epsilon3/4 genotype is associated with decreased risk of premature CHD. Because the results of similar studies are not consistent, it may be that the relationship between apo E genotype and CHD is related to ethnicity rather than a universal phenomenon.

Adult↗