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At least 253 records · Page 14Linked to original sources
PubMed2004

Arachidonate 5-lipoxygenase promoter genotype, dietary arachidonic acid, and atherosclerosis.

BACKGROUND: Leukotrienes are inflammatory mediators generated from arachidonic acid (polyunsaturated n-6 fatty acid) by the enzyme 5-lipoxygenase. Since atherosclerosis involves arterial inflammation, we hypothesized that a polymorphism in the 5-lipoxygenase gene promoter could relate to atherosclerosis in humans and that this effect could interact with the dietary intake of competing 5-lipoxygenase substrates. METHODS: We determined 5-lipoxygenase genotypes, carotid-artery intima-media thickness, and markers of inflammation in a randomly sampled cohort of 470 healthy, middle-aged women and men from the Los Angeles Atherosclerosis Study. Dietary arachidonic acid and marine n-3 fatty acids (including a competing 5-lipoxygenase substrate that reduces the production of inflammatory leukotrienes) were measured with the use of six 24-hour recalls of food intake. RESULTS: Variant 5-lipoxygenase genotypes (lacking the common allele) were found in 6.0 percent of the cohort. Mean (+/-SE) intima-media thickness adjusted for age, sex, height, and racial or ethnic group was increased by 80+/-19 microm (95 percent confidence interval, 43 to 116; P<0.001) among carriers of two variant alleles, as compared with carriers of the common (wild-type) allele. In multivariate analysis, the increase in intima-media thickness among carriers of two variant alleles (62 microm, P<0.001) was similar in this cohort to that associated with diabetes (64 microm, P=0.01), the strongest common cardiovascular risk factor. Increased dietary arachidonic acid significantly enhanced the apparent atherogenic effect of genotype, whereas increased dietary intake of n-3 fatty acids blunted the effect. Finally, the plasma level of C-reactive protein, a marker of inflammation, was increased by a factor of 2 among carriers of two variant alleles as compared with that among carriers of the common allele. CONCLUSIONS: Variant 5-lipoxygenase genotypes identify a subpopulation with increased atherosclerosis. The observed diet-gene interactions further suggest that dietary n-6 polyunsaturated fatty acids promote, whereas marine n-3 fatty acids inhibit, leukotriene-mediated inflammation that leads to atherosclerosis in this subpopulation.

Adult↗
PubMed2006

Associations of classic Kaposi sarcoma with common variants in genes that modulate host immunity.

Classic Kaposi sarcoma (CKS) is an inflammatory-mediated neoplasm primarily caused by Kaposi sarcoma-associated herpesvirus (KSHV). Kaposi sarcoma lesions are characterized, in part, by the presence of proinflammatory cytokines and growth factors thought to regulate KSHV replication and CKS pathogenesis. Using genomic DNA extracted from 133 CKS cases and 172 KSHV-latent nuclear antigen-positive, population-based controls in Italy without HIV infection, we examined the risk of CKS associated with 28 common genetic variants in 14 immune-modulating genes. Haplotypes were estimated for IL1A, IL1B, IL4, IL8, IL8RB, IL10, IL12A, IL13, and TNF. Compared with controls, CKS risk was decreased with 1235T/-1010G-containing diplotypes of IL8RB (odds ratio, 0.49; 95% confidence interval, 0.30-0.78; P = 0.003), whereas risk was increased with diplotypes of IL13 containing the promoter region variant 98A (rs20541, alias +130; odds ratio, 1.88; 95% confidence interval, 1.15-3.08; P = 0.01) when considered in multivariate analysis. Risk estimates did not substantially vary by age, sex, incident disease, or disease burden. Our data provide preliminary evidence for variants in immune-modulating genes that could influence the risk of CKS. Among KSHV-seropositive Italians, CKS risk was associated with diplotypes of IL8RB and IL13, supporting laboratory evidence of immune-mediated pathogenesis.

Adult↗
PubMed2005

Association of GSTP1 polymorphism and survival for esophageal cancer.

PURPOSE: Activity of glutathione S-transferase (GST) is associated with detoxification of xenobiotics and the maintenance of cell viability. Genetically variant GSTs produce different enzymatic activities. The clinical significance of this variation is still puzzling. We investigated whether genetic polymorphisms of GST including GSTP1, GSTM1, and GSTT1 affect survival among esophageal cancer patients. EXPERIMENTAL DESIGN: From 1996 to 2002, 233 patients with pathologically proven esophageal cancer were recruited from the Department of Surgery, National Taiwan University Hospital. GST genotypes, including GSTT1, GSTM1, and GSTP1, were determined by PCR or PCR-RFLP. The influence of the genetic polymorphisms on patient survival was estimated using the method of Kaplan-Meier survival function and Cox proportional hazards models. RESULTS: The mean survival times (months) of the GSTP1 Ile/Ile, Ile/Val, and Val/Val were 11, 10, and 7, respectively (P < 0.05). The more the patients carried GSTP1 variant Val alleles, the poorer the survival rate (adjusted hazard ratio, 1.36; 95% confidence interval, 1.01-1.84; Ptrend = 0.045). In contrast, no association of GSTT1 or GSTM1 genotypes with survival rate was noted. CONCLUSION: The presence of the GSTP1 variant allele (Val) is associated with a poorer prognosis of esophageal cancer.

Adult↗
PubMed2003

Comparison of two cyclosporine formulations in healthy Middle Eastern volunteers: bioequivalence of the new Sigmasporin Microoral and Sandimmun Neoral.

A study was conducted to establish bioequivalence between two oral cyclosporine 100 mg capsules, Sigmasporin Microoral (Gulf Pharmaceutical Industries - Julphar, United Arab Emirates, under technical co-operation with Sigma Pharma, Brazil) and Sandimmun Neoral (Novartis, Switzerland), in a Middle Eastern population, even though both formulations were found to be bioequivalent earlier in a Brazilian population (data on file). It was designed as a randomized, open label, two-way crossover study in which 30 fasting, healthy male volunteers received a single 100 mg cyclosporine dose with 240 ml of water on two treatment days separated by a 1 week washout period. After dosing, serial blood samples were collected for a period of 24 h. Plasma was analyzed for cyclosporine A by a sensitive, reproducible and accurate HPLC method with MS detection capable of detecting cyclosporine A in the range of 5-400 ng/ml with a limit of quantitation of 5 ng/ml. Various pharmacokinetic parameters including AUC(0-t), AUC(0- proportional, variant ), C(max), T(max), T(1/2), and lambda(Z) were determined from plasma concentrations of both formulations. AUC(0-t), AUC(0- proportional, variant ), and C(max) were tested for bioequivalence after log-transformation of data. No significant difference was found based on ANOVA; 90% confidence intervals (82.98-110.57% for AUC(0-t), 81.57-124.71% for AUC(0- proportional, variant ), 80.15-98.91% for C(max)) for these parameters were found to be within the bioequivalence acceptance range of 80-125%. Based on these statistical inferences, it was concluded that Sigmasporin Microoral is bioequivalent to Sandimmun Neoral.

Administration, Oral↗
PubMed2000

An IL13 coding region variant is associated with a high total serum IgE level and atopic dermatitis in the German multicenter atopy study (MAS-90).

BACKGROUND: Allergic diseases are one of the major causes of morbidity in the developed countries today, and the prevalence of these diseases is increasing steadily. Study of total serum gE level is important in understanding the genetics of allergic iseases because IgE levels are considered to be a crucial pathogenic component. IL-13 plays an important role in the induction of IgE synthesis and in the pathogenesis of allergic diseases. OBJECTIVE: We sought to examine potential variation at the IL13 gene and estimate its effect on elevated IgE level and atopic dermatitis (AD). METHODS: We conducted mutational analyses of the IL13 gene by using single-stranded conformation polymorphism and DNA sequencing. Case control studies for high-IgE phenotype and AD were performed by using subjects from the German MAS-90 cohort. RESULTS: A novel IL13 coding region variant at 4257 bp (G to A, fourth exon) was identified. Case control studies of a German sample from the MAS-90 cohort showed significant associations between the presence of the A allele and two atopic phenotypes: high IgE (odds ratio, 2.38; 95% confidence interval, 1.35-4.21; P =.0026) and AD (odds ratio, 1.77; 95% confidence interval, 1.06-2.96; P =.03). CONCLUSION: This IL13 coding region variant may be involved in the pathogenesis of AD and high total serum IgE level in a study population of white subjects.

Chromosomes, Human, Pair 5↗
PubMed2004

A population-based case-control study of the XRCC1 Arg399Gln polymorphism and susceptibility to bladder cancer.

Cigarette smoking is the major cause of bladder cancer. Constituents in tobacco smoke can induce oxidative DNA damage requiring base excision repair. The Arg399Gln polymorphism in the DNA base excision repair gene XRCC1 is associated with several phenotypic markers of reduced DNA repair capacity. Results from several epidemiologic studies suggest that the Arg399Gln polymorphism may influence susceptibility to several cancers including bladder cancer; however, data from large population-based studies are lacking. In a population-based case-control study from New Hampshire, we observed a reduced risk among those homozygous for the Arg399Gln XRCC1 variant polymorphism compared with those with one or two wild-type alleles (odds ratio 0.6, 95% confidence interval 0.4-1.0). There was no indication of a gene-environment interaction between cigarette smoking and the variant genotype. Our data are consistent with a potential role of the XRCC1 Arg399Gln polymorphism in bladder cancer susceptibility and further suggest that there may be DNA lesions important in bladder carcinogenesis, repaired by the base excision repair mechanism, that are not directly associated with tobacco smoking.

Age Distribution↗
PubMed1999

Association of the NAD(P)H:quinone oxidoreductase 609C-->T polymorphism with a decreased lung cancer risk.

The NAD(P)H:quinone oxidoreductase gene, NQO1, often carries a C-->T transition at bp 609, which has been associated with a reduced enzymatic activity and which may result in altered metabolic activation of tobacco smoke procarcinogens. We tested the association of this polymorphism with lung cancer risk in a population-based case-control study of 327 cases and 440 controls of Caucasian, Japanese, or Native Hawaiian ancestry in Hawaii. We found a notable difference in the frequency of the variant allele among Japanese (38%), Caucasians (20%), and Hawaiians (22%). Overall, the variant allele was less frequent in cases than in controls (P = 0.03). A significant inverse association was found in Japanese, with adjusted odds ratios of 0.8 (95% confidence interval, 0.4-1.5) and 0.3 (0.1-0.7) for the heterozygous and homozygous variant genotypes, respectively, compared with the homozygous wild-type genotype (P for genetic trend, 0.02). The association did not reach statistical significance in Caucasians and Hawaiians but was in the same direction.

Alleles↗
PubMed2006

Genetic polymorphisms in glutathione S-transferases T1, M1 and P1 and susceptibility to reflux esophagitis.

Recent studies indicate that the prevalence of reflux esophagitis (RE) in China is increasing. RE is one of the most common esophageal complications associated with gastroesophageal reflux disease (GERD) and RE-Barrett's esophagus-esophageal adenocarcinoma (EAC) sequence has been considered as an histogenesis model for EAC in Western countries. RE is only present in a subset of patients with GERD, suggesting an altered susceptibility to RE may exist in these GERD individuals. However, the genetic changes related with high susceptibility to RE is largely unknown. The polymorphisms in glutathione S-transferases (GSTs) T1, M1 and P1 have been reported with high susceptibity to esophageal cancer in Chinese people. The present case-control study was thus undertaken to characterize the genetic polymorphisms of GSTs and their correlation with susceptibility to RE. One hundred and nine patients with RE, 97 patients with nonerosive reflux disease (NERD) and 97 normal controls were recruited in this study. All the subjects were from Beijing, China, and received endoscopic examination and questionnaires for RE. Genomic DNA was extracted from the lymphocytes of peripheral blood for each subject. Genotypes of the GSTM1 and GSTT1 genes were analyzed by a multiplex PCR method. A-->G polymorphism of codon 104 of the GSTP1 gene was detected using PCR-based restriction fragment length polymorphisms (RFLP). The variant GSTP1 genotypes (*A/*Bomicron*B/*B) was found with a high frequency in the case with RE (40%), and followed by NERD (25%) and normal control (22%). The differences were statistically significant (P < 0.05). The risk for RE increased 2.42-fold [odds ratio (OR); 95% confidence interval (95% CI), 2.42 (1.22-4.80)] in the subjects with variant GSTP1 genotype. The subjects with positive variant GSTP1 genotypes and negative H. pylori infection showed increasing tendency for risk of RE [OR (95% CI), 2.67 (1.06-6.70)]. However, the subjects with GSTT1 and GSTM1 polymorphisms did not show any correlation with high risk for RE or NERD. No significant interactions were identified between the variant GSTs and cigarette smoking, or alcohol drinking and subtype of RE. The present result suggests that GSTP1 genetic polymorphism may be one of the high susceptibility factors involved in the mechanisms of RE. H. pylori infection may play a protective role against RE.

Case-Control Studies↗
PubMed2006

Inflammatory cytokine gene polymorphisms, nonsteroidal anti-inflammatory drug use, and risk of adenoma polyp recurrence in the polyp prevention trial.

BACKGROUND: Pro- and anti-inflammatory cytokine genes may be important in the maintenance and progression of colorectal cancer. It is possible that single-nucleotide polymorphisms in inflammatory genes may play a role in chronic colonic inflammation and development of colorectal adenomas. Furthermore, common variants in cytokine genes may modify the anti-inflammatory effect of nonsteroidal anti-inflammatory drugs (NSAIDs) in the prevention of colorectal cancer. METHODS: We examined the association between cytokine gene polymorphisms and risk of recurrent adenomas among 1,723 participants in the Polyp Prevention Trial. We used logistic regression to calculate odds ratios (OR) for the association between genotype, NSAID use, and risk of adenoma recurrence. RESULTS: Cytokine gene polymorphisms were not statistically significantly associated with risk of adenoma recurrence in our study. We observed statistically significant interactions between NSAID use, IL-10 -1082 G>A genotype, and risk of adenoma recurrence (P = 0.01) and multiple adenoma recurrence (P = 0.01). Carriers of the IL-10 -1082 G>A variant allele who were non-NSAID users had a statistically significant decreased risk of multiple adenoma recurrence (OR, 0.43; 95% confidence interval, 0.24-0.77) as well as a nonsignificant 30% decreased risk of any adenoma recurrence. In contrast, NSAID users who were carriers of the IL-10 -1082 G>A variant allele were at an increased risk of any adenoma recurrence (OR, 1.55; 95% confidence interval, 1.00-2.43). CONCLUSION: These findings suggest that individuals who are carriers of the IL-10 -1082 G>A variant allele may not benefit from the chemoprotective effect of NSAIDs on adenoma polyp recurrence.

Adenomatous Polyps↗
PubMed2000

Positive association of endothelial nitric oxide synthase gene polymorphism with hypertension in northern Japan.

Vascular endothelial cells produce nitric oxide (NO), which contributes to the regulation of blood pressure and regional blood flow. Although Endothelial NO synthase (eNOS) gene polymorphisms have been shown to have a positive association with coronary artery disease, the linkage between eNOS gene polymorphisms and hypertension has been controversial. In the present study, therefore, we identified genotypes for Glu298Asp and variable number tandem repeats in intron 4 (4b/a) in 183 hypertensive and 193 normotensive populations. The Glu298Asp variant had a significant association with hypertension (odds ratio, 1.8; 95% confidence interval, 1.1-3.0). The allele frequencies of 298Asp for Glu298 in hypertensive patients were significantly higher than those in normotensive subjects (0.128 vs 0.080, p<0.05). Diastolic and mean arterial blood pressures were significantly higher in hypertensive subjects with the 298Asp allele than those without the variant allele (p<0.05). However, disequilibrium of 4b/a polymorphism was absent between these two groups. These results suggest that the Glu298Asp variant may be a genetic susceptibility factor for hypertension.

Aged↗
PubMed2001

ELAC2/HPC2 involvement in hereditary and sporadic prostate cancer.

The ELAC2/HPC2 gene at 17p11 is the first candidate gene identified for human prostate cancer (PRCA) based on linkage analysis and positional cloning (S. V. Tavtigian et al. Nat. Genet., 27:172-180, 2001). A truncating mutation was found in one hereditary prostate cancer (HPC) family, whereas two missense variants, Ser217Leu and Ala541Thr, were reported to be associated with increased PRCA risk in the general population. Here, we screened for mutations of the ELAC2/HPC2 gene in 66 Finnish HPC families. Several sequence variants, including a new exonic variant (Glu622Val) were found, but none of the mutations were truncating. We then analyzed the frequency of the three found missense variants in 1365 individuals, including hereditary (n = 107) and unselected (n = 467) PRCA, benign prostatic hyperplasia (n = 223), and population controls (568 healthy male blood donors). Ser217Leu and Ala541Thr variants carried no significantly elevated risk for HPC or PRCA, although the latter variant was associated with benign prostatic hyperplasia. The previously undescribed Glu622Val variant had a 1.0% population prevalence, but a significantly higher frequency in PRCA cases (3.0% odds ratio, 2.94; 95% confidence interval, 1.05-8.23). We conclude that ELAC2/HPC2 truncating mutations are rare in HPC, but that rare variants of the ELAC2/HPC2 require additional study as risk factors for PRCA in the general population.

Aged↗
PubMed2004

The SOD2 Val/Val genotype enhances the risk of nonsmall cell lung carcinoma by p53 and XRCC1 polymorphisms.

BACKGROUND: Exogenous reactive oxygen species (ROS) induces DNA damage. Manganese superoxide dismutase (SOD2) catalyzes the dismutation of superoxide radicals, a major type of ROS, into hydrogen peroxide. p53 is a tumor suppressor gene, and X-ray cross-complementing group 1 (XRCC1) is involved in the base-excision repair of ROS-induced DNA damage. METHODS: The authors investigated whether the SOD2 Ala16Val polymorphism modifies the associations between p53 Arg72Pro and XRCC1 Arg399Gln polymorphisms and the risk of nonsmall cell lung carcinoma (NSCLC) in a case-control study of 935 Caucasian patients with NSCLC and 1233 healthy control participants. The results were analyzed using logistic regression models that were adjusted for possible confounding variables. RESULTS: There was no association between p53 or XRCC1 polymorphism and NSCLC risk for individuals with SOD2 Ala/Ala or Ala/Val genotype. For individuals with the SOD2 Val/Val genotype, greater risks were found in association with p53 (variant Pro allele vs. Arg/Arg), XRCC1 (variant Gln allele vs. Arg/Arg), and the combination of the two polymorphisms ("double variant" vs. "double wild type"), with the adjusted odds ratios (ORs) of 1.84 (95% confidence interval [95% CI], 1.20-2.82), 1.39 (95% CI, 0.98-2.21), and 2.54 (95% CI, 1.38-4.68), respectively. Furthermore, the greater risk for the double variant of p53 and XRCC1 in the SOD2 Val/Val genotype group was specific only for patients with adenocarcinoma and not for patients with squamous cell carcinoma, with adjusted ORs of 3.31 (95% CI, 1.68-6.51) and 0.69 (95% CI, 0.24-2.02), respectively. CONCLUSIONS: The SOD2 Val/Val genotype may increase the risk of NSCLC carried by XRCC1 and p53 polymorphisms, particularly for adenocarcinoma.

Adult↗
PubMed2000

A variant of the glucocorticoid receptor gene is not associated with adrenal androgen excess in women with polycystic ovary syndrome.

OBJECTIVE: To determine whether the frequency of the N363S variant of the glucocorticoid receptor (GRL) was increased in women with PCOS and adrenal androgen (AA) excess. DESIGN: Prospective case-control study. SETTING: University reproductive endocrinology laboratory and outpatient clinic. PATIENT(S): Consecutive patients of non-Hispanic white race diagnosed with PCOS (n = 114) and healthy controls (n = 92). INTERVENTION(S): Blood and DNA sampling before hormonal therapy. MAIN OUTCOME MEASURE(S): PCOS patient and healthy control genotypes, with the N363S allele representing a variant of GRL. RESULT(S): Fifty-four PCOS patients with (DHEAS > or = 3000 ng/mL) and 55 without (DHEAS < or = 2,500 ng/mL) AA excess, respectively, were studied. Six of 109 (5.5%) patients studied were found to be heterozygous carriers of the A-->G base pair substitution at cDNA position 1220, resulting in the missense mutation N363S. Of these six, four had excessive AA secretion (i.e., excess DHEAS levels). There was no significant difference in the allele frequency of the GRL variant between PCOS patients with and without AA excess and controls (3.7% [95% confidence interval: 1.0%-5.7%], 1.8% [0.2%-6. 0%], and 3.3% [2.3%-6.0%]). None of the subjects were found to be homozygous for the N363S allele. CONCLUSION(S): The N363S variant of GRL was an uncommon occurrence in our population of healthy women and PCOS patients and did not appear to play a major role in the genetic predisposition to PCOS or to AA excess in PCOS.

Adrenal Glands↗
PubMed2002

The double heterozygote of two endothelin-1 gene polymorphisms (G8002A and -3A/-4A) is related to big endothelin levels in chronic heart failure.

The aim of this study was to focus on the relationship among the associated genotypes of G (8002) A and -3A/-4A endothelin-1 (ET-1) gene polymorphisms and some clinical and/or biochemical parameters in Czech (Caucasian) patients with chronic heart failure. Included in the study were 103 patients with chronic heart failure (functional classes NYHA II-IV, ejection fraction < 40%). The ET-1 gene polymorphisms were detected by polymerase chain reaction (PCR) and restriction fragment length polymorphism methods. A significant decrease in the ET-1-associated genotype AG3A4A number (double heterozygote) was observed in CHF patients with plasma big endothelin levels above 0.7 pmol/L compared to those with levels below 0.7 pmol/L (OR = 0.19; 95% confidence interval = 0.06-0.57; P = 0.005; Pcorr = 0.03). We found a significant decrease in the AG3A4A genotype number in the other groups compared to the group of patients with both big endothelin and endothelin-1 levels under 0.7 pmol/L (OR = 0.22; 95% confidence interval = 0.07-0.79; P = 0.02). The double heterozygote variants of two ET-1 gene polymorphisms were associated with significantly less risk for chronic heart failure with higher levels of big endothelin.

Adult↗
PubMed2026

Precision ID mtDNA Whole Genome Panel and sequencing of telogen hairs - perspectives for validation and implementation in casework.

Shed hair is a commonly encountered type of forensic evidence. Shed telogen hairs generally contain insufficient or highly degraded nuclear DNA for STR profiling; however, mtDNA analysis of telogen hair and hair shafts remains possible. We validated whole mitochondrial genome (mtGenome) sequencing using the Precision ID mtDNA Whole Genome Panel (Thermo Fisher Scientific) and subsequently implemented the panel for the analysis of telogen hair, buccal, and casework samples. We analysed 90 diluted DNA samples containing 3-3,600 mtDNA copies, shed telogen hairs and their corresponding mtDNA from buccal swabs from 91 individuals, and 11 archived DNA extracts from hair samples in criminal cases. Complete mtGenome sequences were consistently recovered in 99% of samples across DNA dilution series at DNA input levels as low as 47 mtDNA copies, demonstrating the assay's robustness under low-template conditions. We obtained complete and reproducible mtGenome sequences with &#x2265;&#x2009;327 mtDNA copies/&#xb5;L from telogen hair samples. After applying ISFG recommendations and excluding low-confidence discrepancies associated with high-strand bias, heteroplasmic variants and sequencing artifacts, mtGenome sequence concordance increased from 93.4% to 100%. None of the 16 negative controls produced complete mtDNA sequences. Six negative controls showed low-level mtDNA signal (2-8 variants), consisting predominantly of common polymorphisms. These samples did not yield complete mtGenome sequences and showed no correspondence to any of the analysed samples. Finally, archived telogen hair samples from criminal cases presented complete mtGenome sequences with an average read depth of 1,037x.Our findings highlight the reliability of mtDNA analysis of telogen hairs using the Precision ID mtDNA Whole Genome Panel for implementation in forensic casework.

Forensic casework↗
PubMed2006

Subsets of SNPs define rare genotype classes that predict ischemic heart disease.

Single nucleotide polymorphisms (SNPs) are hypothesized to explain the genetic predisposition to ischemic heart disease (IHD) in the general population. Lack of evidence for a role of such variation is fostering pessimism about the utility of genetic information in the practice of medicine. In this study we determined the utility of exonic and 5' SNPs in apolipoprotein E (APOE) and lipoprotein lipase (LPL) when considered singly and in combination for predicting incidence of IHD in 8,456 individuals from the general population during 24 years of follow-up. In men, LPL D9N improved prediction of IHD (P = 0.03) beyond smoking, diabetes and hypertension. The group of men heterozygous and homozygous for the rare D9N variant had a hazard ratio (HR) of 1.69 (95% confidence interval = 1.10-2.58) relative to the most common genotype. Pairwise combinations of D9N with -219G > T in APOE and N291S and S447X in LPL significantly improved the prediction of IHD (P = 0.05 in women, P = 0.04 in men, P = 0.03 in men, respectively) beyond smoking, diabetes and hypertension, and identified subgroups of individuals (n = 6-94) with highly significant HRs of 1.92-4.35. These results were validated in a case-control study (n = 8,806). In conclusion, we present evidence that combinations of SNPs in APOE and LPL identify subgroups of individuals at substantially increased risk of IHD beyond that associated with smoking, diabetes and hypertension.

Adult↗
PubMed2006

GPX1 Pro198Leu polymorphism, interactions with smoking and alcohol consumption, and risk for lung cancer.

We genotyped blood samples from 432 lung cancer cases and 798 persons in a comparison group and examined the role of the GPX1 (Pro198Leu, rs1050450) polymorphism and interactions with external exposures in the development of lung cancer. The incidence rate ratio for lung cancer was 0.60 (95% confidence interval: 0.35-1.05) when homozygous carriers of the variant allele were compared with the homozygous carriers of the wild type, and the risk for lung cancer was significantly lower among participants carrying more variant alleles (p-trend=0.03). We found stronger associations between several smoking variables and alcohol intake and lung cancer risk among GPX1(TT) carriers than among GPX1(CC) and GPX1(CT) carriers.

Alcohol Drinking↗
PubMed2003

Polymorphisms in the melanocortin-1 receptor (MC1R) and agouti signaling protein (ASIP) genes in Korean vitiligo patients.

We have examined the frequency of SNP polymorphisms within the melanocortin-1 receptor (MC1R) and agouti signaling protein (ASIP) genes in 114 Korean vitiligo patients and 111 normal controls to assess the association of these loci with vitiligo risk. Using direct sequencing techniques, we found the following five MC1R coding region SNPs: Arg67Gln (G200A), Val92Met (G274A), Ile120Thr (T359C), Arg160Arg (C478A), and Gln163Arg (A488G). Of these, the most common were Val92Met at 14% in patients vs. 9% in controls (P = 0.17) and Gln163Arg at 17% in patients vs. 17% in controls (P = 0.84). Presence of the A allele of Val92Met (G274A) was higher in vitiligo patients [P = 0.12, odds ratio (OR) [95% confidence interval (CI)] = 1.68 (0.86-3.25)]. The other three variants showed a frequency <5% of both patients and controls. The ASIP 3'UTR genotype (g.8818A-G) was also assessed in the same subjects. The frequency of the G allele of 3'UTR in ASIP was 17% in vitiligo and 12% in controls [P = 0.14, OR (95% CI) = 1.49 (0.87-2.54)]. Carriage of the G allele was higher in vitiligo patients [P = 0.17, OR (95% CI) = 1.50 (0.83-2.72)], and those who also carried MC1R Val92Met were more prone to vitiligo [eight of 111 patients vs. four of 111 in controls, P = 0.14, OR (95% CI) = 2.75 (0.71-8.69)]. None of these associations, however, reached statistical significance.

Agouti Signaling Protein↗