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Increased risk of prostate cancer associated with AA genotype of cyclin D1 gene A870G polymorphism.

CCND1 mRNA is alternatively spliced to produce 2 transcripts, and the splicing pattern may be modulated by a frequent A870G single-nucleotide polymorphism within the conserved splice donor site of exon 4. Several studies have suggested a significant association between the CCND1 genotype and onset or progression of various cancers. To investigate the correlation of the polymorphism with genetic susceptibility to PCa and its disease status, we examined the polymorphism in 214 cases of PCa, 234 cases of BPH and 254 male controls. The CCND1 A allele was more frequently observed in the PCa group (p = 0.015) and the BPH group (p = 0.018) than the control group. Men with the AA genotype had an increased risk of PCa (aOR = 1.93, 95% CI 1.13-3.30, p = 0.016) and BPH (aOR = 1.84, 95% CI 1.09-3.09, p = 0.023) compared to those with the GG genotype. No significant association was observed when men with the AG genotype were compared to those with the GG genotype (PCa: aOR = 1.00, 95% CI 0.65-1.54, BPH: aOR = 0.91, 95% CI 0.60-1.39). The risk of PCa associated with the AA genotype appeared to be stronger in men aged 73 years or younger (aOR = 2.89, 95% CI 1.38-6.01, p = 0.005), whereas no association was found in men older than 73 years (aOR = 1.02, 95% CI 0.44-2.34). No significant difference in genotype frequency was found among patients with low-, intermediate- and high-grade tumors (p = 0.730) or between patients with localized and metastatic PCa (p = 0.679). However, in patients with high-grade or metastatic PCa, a significantly increased risk associated with the AA genotype compared to controls was observed, while no significant results were found in those with low/intermediate or localized PCa. The A allele of the CCND1 A870G polymorphism was recessively associated with susceptibility to PCa and BPH in a Japanese population, giving a 2-fold increased risk of PCa and BPH in men with the AA genotype compared to those with the GG genotype. Although the risk of PCa associated with the AA genotype appeared to contribute especially to men aged 73 years or younger and the A allele may be associated with disease status of PCa, these conjectures require validation in future studies on a larger number of subjects.

Adenocarcinoma↗

Genotyping of hepatitis C virus isolates by a modified polymerase chain reaction assay using type specific primers: epidemiological applications.

A polymerase chain reaction (PCR)-based assay using primers against the hepatitis C core gene has been described [Okamoto et al. (1992a): Journal of General Virology 73:673-679]. Within the two major HCV genotypes 1 and 2, the Okamoto system identifies two subtypes each (1a, 1b and 2a, 2b, respectively). Typing is achieved by a primary PCR with consensus primers followed by a nested PCR with type specific primers. The original assay was modified by addition of a parallel second PCR identifying the recently described major genotype 3. The assay also identifies in duplicate subtype 1b (type II by Okamoto), suggested to respond poorly to interferon. Reaction conditions were reviewed and melting temperatures of all typing primers equalised to increase strigency. The modified system functioned well and typing results were supported by partial core sequencing. The following distribution of genotypes was found in 53 hepatitis C virus (HCV) infected Swedish blood donors: genotype 1a (57%), 3 (19%), 1b (13%), and 2b (11%). In six recipients of HCV infected blood identified in a retrospective study, the recipient HCV genotype was identical to donor HCV genotype. Furthermore, in HCV positive couples identical genotype was observed when only one partner had an external risk factor; whereas genotypes were often diverse if both sex partners had parenteral risk factors. Finally, a cluster of hepatitis C cases in a haemodialysis unit was evaluated retrospectively. Eight patients had genotype 1b, two had mixed 1a and 1b, and one had type 1a. The modified HCV genotyping assay was of value in examining different epidemiological situations and can be expanded presumably to include future genotypes.

Base Sequence↗

Molecular epidemiology of mumps virus in Japan and proposal of two new genotypes.

We isolated 872 strains of mumps virus from naso-pharyngeal secretions in seven different districts of Japan from January 2000 to July 2001. Among them, 57 strains were geno-typed by nucleotide sequencing in part of the hemagglutinin-neuraminidase (HN) and small hydrophobic (SH) protein regions. Four different genotypes (B, G, K, and L) of mumps virus were co-circulating in Japan and the distribution of genotypes varied in geographically different districts. Two new clusters designated as genotypes K and L had more than 7% nucleotide variation in the SH gene. Among the 57 strains, 11 were classified as B, 35 as G, three as K, and eight as L, which was mainly isolated in Tokyo. We also examined 104 stains isolated in a clinic in Mie prefecture from 1993 to 2003. Genotype B was the indigenous strain and genotype K was introduced in 1994. Genotypes B and K co-circulated in the 1990s and were replaced by genotype G in 2000. There was no significant change in neutralizing test antibody titers against genotypes B, G, K, and L using seven post-vaccination sera with Hoshino strain (genotype B) and these four genotypes had a different antigenicity from genotype A. We should continue to watch on mumps virus molecular epidemiology.

Amino Acid Sequence↗

Reliability of hepatitis C virus core antigen assay for detection of viremia in HCV genotypes 1, 2, 3, and 4 infected blood donors: a collaborative study between Japan, Egypt, and Uzbekistan.

Nucleic acid amplification-based methods are used for confirmation of viremia in antibody to hepatitis C virus (anti-HCV)-positive patients. However, this technology is labor intensive, time consuming, requires complex laboratory conditions, and expensive. The aim of this study was to evaluate the sensitivity and specificity of the HCV core antigen (HCVcAg) assay as an alternative approach for confirmation of viremia in HCV-infected subjects with HCV genotype 1-4. Two hundred forty-six asymptomatic HCV RNA- positive donors were enrolled in this study, consisting of 122 blood donors from Egypt (116 with genotype 4, 4 with genotype 1, and 2 with 1 + 4 genotypes), 109 from Japan (85 with genotype 1, and 24 with genotype 2), and 15 from Uzbekistan (all with genotype 3). A total of 234 (95.1%) of 246 RNA-positive specimens were detected by the HCVcAg assay; the sensitivity of HCVcAg assay consisted 93.4, 100, 100, and 94.8% for genotypes 1, 2, 3, and 4, respectively in comparison with RT-PCR assay. The specificity of the assay was confirmed in the absence of the false-positive results among 53 anti-HCV-negative, but anti-Schistosoma mansoni (anti-Sm) positive donors from Egypt. A positive correlation between HCVcAg and HCV RNA concentration levels (r = 0.671, P < 0.05) was observed among specimens with HCV genotype 4. The mean HCVcAg level was significantly lower in specimens with genotype 4 (2,935 fmol/L) comparing to genotypes 1, 2, and 3 (5,034, 4,962, and 4,740 fmol/L, respectively). No specific mutation was found in the core-encoding region of the studied specimens. In conclusion, HCVcAg is shown to be specific, sensitive, and informative qualitative index for HCV viremia in asymptomatic carriers.

Amino Acid Sequence↗

Characterization of seven genotypes (A to E, G and H) of hepatitis B virus recovered from Japanese patients infected with human immunodeficiency virus type 1.

To investigate the prevalence of hepatitis B virus (HBV) genotypes and characteristics of HBV isolates among Japanese patients infected with human immunodeficiency virus type 1 (HIV), serum samples collected between September 1990 and March 2002 from 471 HIV-infected patients (age, 38.8 +/- 11.4 [mean +/- standard deviation] years; male, 90%) were tested for hepatitis B surface antigen (HBsAg) and HBV DNA. Positivity for HBsAg and HBV DNA was seen in 42 patients (8.9%), 41 of whom had contracted HIV infection through sexual activity and 1 had hemophilia. Genotypes of HBV were determined by comparative and phylogenetic analyses of the S gene sequence (396 nucleotides [nt]). The distribution of HBV genotypes among the 42 HBV-viremic patients was: A (50%), B (5%), C (24%), D (5%), E (2%), H (10%), A plus D (2%), A plus G (2%). The hemophilia patient had HBV genotype D. Genotypes E, G, and H which had not been reported in Japan, were found in one patient each who had traveled to Zambia, the US, and South America, respectively. Genotypes A and D, which are rare in Japan, were found in patients who had no history of traveling abroad. The entire genome of the HB-JI411 (genotype E [3,212 nt]), HB-JI444G (genotype G [3,248 nt]), and HB-JI260 (genotype H [3,218 nt]) isolates had the highest identity of 98.3%, 99.9%, and 98.5%, respectively, with reported HBV isolates of the same genotype. Most Japanese patients coinfected with HIV and HBV had HBV genotypes that are found rarely or had not been reported in Japan.

Adult↗

Changing prevalence of hepatitis B virus genotypes in Iceland.

At present eight hepatitis B virus (HBV) genotypes have been characterized: A to H. The most common genotype in Northern Europe is genotype A. So far there is no record of the specific HBV genotype distribution in Iceland. Iceland has a small population whose homogeneity has changed due to increasing migration during the past decades. The distribution of HBV genotypes in Iceland was analyzed using sera from 170 Icelandic patients. The samples were obtained before 1989, during an HBV epidemic among intravenous drug users in 1989 to 1992 and after 1994. A fragment of the HBV S-gene was amplified, sequenced and subjected to phylogenetic analysis. Among samples derived before 1989 genotypes A, C, and D were found. Most of the samples diagnosed during the epidemic belonged to genotype D and a smaller portion to genotype A. This suggests that the epidemic was most likely caused either by an endogenous HBV strain or by a strain imported from Europe or the USA. Among samples obtained after 1994, genotypes A to E and G were found, but the majority were of genotypes A, C, and D. This is consistent with an increase in migration and immigration from regions in Asia and Africa during the past 10 years. Thus, the changing prevalence of HBV genotypes in a small isolated community such as Iceland reflects the influence of migration and increasing contacts with regions outside the Western World.

DNA, Viral↗

Hepatitis B virus genotyping, core promoter, and precore/core mutations among Afghan patients infected with hepatitis B: a preliminary report.

In spite of hepatitis B virus (HBV) vaccination, HBV infection remains an important public health problem worldwide. Although the HBV genotype distribution has been determined in some parts of South Central Asia, no survey has been conducted to determine the HBV genotype in Afghanistan. Twelve Afghan patients infected with HBV living in Afghanistan were enrolled in this study. Partial HBsAg and basic core promoter, precore, and core (BCP/preC/C) regions were amplified and subjected for direct sequencing. In parallel, precore G1896A mutation was also determined by an amplification-created restriction site method. Results revealed HBV genotype D (95% bootstrap value), sub-genotype D1 (98% bootstrap value), and subtype ayw2 in all Afghan isolates. Afghan isolates clustered in a separate branch in the D1 sub-genotype called D1', while supported by 82% bootstrap value. The percentage of intra-genotypic distance among Afghan isolates was 1.05% and inter-genotypic distance with the other genotype D was 2.87% and with other genotypes was 7.50%-11.1%. The wild-type, mixed infection, and precore mutant were found in six, two, and four HBV isolates, respectively. The A1762T/G1764A BCP dual mutation was found in one isolate. Three isolates presented single mutation in the BCP dual mutation region, whereas two showed a novel G1764T mutation. In conclusion, this preliminary study revealed HBV genotype D, sub-genotype D1, and subtype ayw2 of HBV among hepatitis B infected patients from Afghanistan. Further investigation should be carried out.

Adolescent↗

Accumulation of phytate in vegetable-type soybean genotypes harvested at four developmental stages.

A total of 17 vegetable-type soybean (Glycine max [L.] Merr) genotypes were planted in four-row plots arranged in a randomized complete block design in 1988 and 1989 at Petersburg, Virginia. Each genotype was harvested at four developmental stages and evaluated for phytate content. Highly significant differences for phytate content were observed among the stages of harvest and genotypes, and there was an interaction between genotype x stage of harvest. The significant differences observed for phytate content among genotypes indicated that genetic variation exists among the tested genotypes for selection and improvement through hybridization. Among the genotypes, 'Kingston' and PI 423852 had the highest phytate content in most stages of harvest while PI 416771, 'Emperor', and PI 416982 had the lowest phytate values. A heritability estimate of 81 percent was observed for phytate content. This high heritability value indicates that selecting genotypes for lower phytate content would be effective. Significant correlations were observed for phytate content among genotypes harvested at R6, R7, R8, and overall. The magnitude of association of R6 with the overall phytate mean was especially high. These results illustrate that determining the phytate content of genotypes at the R6 growth stage would be a good predictor of the overall genotypic performance.

Food Analysis↗

Correlation between vitamin D receptor genotypes and bone mineral density in Japanese patients with osteoporosis.

In order to better understand the pathogenesis of osteoporosis, we investigated the correlation between the vitamin D receptor (VDR) genotypes defined by BsmI restriction enzyme, as well as other related factors, and the bone mineral density (BMD) at the lumbar spine in 90 Japanese patients with osteoporosis. The same study was performed in 36 patients with osteoarthrosis of the hip joint and 92 healthy volunteers. The majority of the VDR genotypes were bb, and a few of the population showed either the BB or Bb genotype in all three groups. There was no statistical difference in the frequencies of these VDR genotypes in the three groups. The mean age-matched value of BMD (Z scores) at the lumbar spine in patients with osteoporosis was significantly lower than that in patients with osteoarthrosis or healthy volunteers. The mean Z scores of the healthy volunteers with bb genotype were significantly higher than those with BB genotype, whereas those of the osteoporosis patients with BB genotype were significantly higher than those with Bb genotype. There was no significant difference in the mean Z scores between bb and Bb genotypes in patients with osteoporosis and healthy volunteers. No significant difference was seen in the mean Z scores in patients with osteoarthrosis regardless of genotype. On the other hand, body weight significantly correlated with BMD in patients with osteoporosis by simple- and multiple-regression analysis. These results indicate that the BMD at the lumbar spine in Japanese patients with osteoporosis is affected by body weight, and might be affected partially by the VDR genotypes defined by BsmI.

Adult↗

Combined effect of GSTM1, GSTT1, and COMT genotypes in individual breast cancer risk.

Our previous studies suggested that both catechol O-methyl transferase (COMT) and glutathione S-transferase (GST) M1 and T1 genotypes are associated with breast cancer risk. Here we extended the studies to evaluate the potential combined effect of these genotypes in individual breast cancer risk. Incident breast cancer cases (n = 202) and controls (n = 299) with no previous cancer were recruited from three teaching hospitals in Seoul in 1996-1999. Information on putative risk factors was collected by interviewed questionnaire. PCR-based methods were used for the genotyping analyses. Odds ratios (ORs) and 95% confidence (CIs) intervals were estimated by unconditional logistic regression after adjustment for known or suspected risk factors of breast cancer. Among pre-menopausal women the low activity associated (COMT *L) allele containing genotypes and the GSTM1 null genotype posed increased risks of breast cancer with ORs of 1.7 (95% CI = 1.0 - 2.8) and 1.7 (95% CI = 1.0-2.8), respectively. A marginally significant effect of GSTT1 null genotype was also observed when the total study population was considered (OR = 1.3, 95% CI = 1.0-2.1). When the combined genotype effects were examined, the concurrent lack of GSTM1 and GSTT1 genes posed a more than 2-fold risk of breast cancer (OR = 2.2, 95% CI = 1.2-3.9); this effect was mainly attributable in pre-menopausal women (OR = 3.2, 95% CI = 1.5-7.2). Moreover, the breast cancer risk increased in parallel with the number of COMT , GSTM1 , and GSTT1 at-risk genotypes (p for trend = 0.003). This association was particularly clear in pre-menopausal women among whom combination of all three high-risk genotypes posed a 4.1-fold breast cancer risk (95% CI = 1.4-12.7) compared with pre-menopausal women without at-risk genotypes (p for trend = 0.001). The trend was more pronounced in women with BMI greater than 22 kg/m2 (p for trend < 0.001) and high-risk status of parity factor (nulliparous or women with the first full term pregnancy at age of over 25-year-old) (p for trend = 0.013). These results suggest the combined effect between reproductive factors and GSTM1, GSTT1 and COMT genotypes in human breast carcinogenesis.

Adult↗

Intra- and inter-genotypic size variation in the central variable region of the 9RL open reading frame of diverse African swine fever viruses.

African swine fever (ASF) viruses are characterised by numerous p72 genotypes, but by low levels of intra-genotypic variation, particularly in domestic pig associated genotypes. As it is precisely these viral lineages that are involved in outbreaks of the disease it is imperative that alternative, more informative gene regions be identified which are suitable for intra-genotypic resolution of relationships. To this end, the central variable region (CVR) of the 9RL open reading frame of diverse ASF viruses was amplified and product sizes scored and compared within and between genotypes. Results indicate that although product sizes are not genotype restricted, there is a high degree of intra-genotypic size variation particularly within the homogeneous p72 genotypes. Within one such genotype, the ESACWA virus genotype, 12 size-discrete CVR products were identified, four corresponding to viruses of west African origin and eight to viruses from countries where the disease is exotic, namely Europe, South America and the Caribbean. The high degree of size heterogeneity in the CVR of this genotype is significant and attests to the usefulness of the CVR gene marker in elucidating the epidemiology of African swine fever.

Africa↗

Methylenetetrahydrofolate reductase and thymidylate synthase genotypes and risk of acute graft-versus-host disease following hematopoietic cell transplantation for chronic myelogenous leukemia.

Methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) play key roles in intracellular folate metabolism. Polymorphisms in these enzymes have been shown to modify toxicity of methotrexate (MTX) after hematopoietic cell transplantation. In this study, we evaluated the risk of acute graft-versus-host disease (GVHD) associated with genetic variation in recipient and donor MTHFR and TS genotypes to assess whether genotype alters the efficacy of MTX in acute GVHD prophylaxis. Data on the transplantation course were abstracted from medical records for 304 adults who received allogeneic hematopoietic cell transplants. MTHFR (C677T and A1298C) and TS (enhancer-region 28-base pair repeat, TSER, and 1494del6) genotypes were determined using polymerase chain reaction/restriction fragment length polymorphism and TaqMan assays. Multivariable logistic regression was used to assess the associations between genotypes and risk of acute GVHD. Compared with recipients with the wild-type MTHFR 677CC genotype, those with the variant 677T allele showed a decreased risk of detectable acute GVHD (677CT: odds ratio, 0.8; 95% confidence interval, 0.4-1.6; 677TT: odds ratio, 0.4; 95% confidence interval, 0.2-0.8; P for trend = .01). The variant MTHFR 1298C allele in recipients was associated with an increased risk of acute GVHD compared with the wild-type MTHFR 1298AA genotype (1298AC: odds ratio, 2.0; 95% confidence interval, 1.1-3.9; 1298CC: odds ratio, 3.6; 95% confidence interval, 1.0-12.7; P for trend < .01). No association with risk of acute GVHD was observed for donor MTHFR genotypes or for recipient or donor TS genotypes, with the exception of an increase in acute GVHD among recipients whose donors had the TSER 3R/2R genotype (odds ratio, 3.0; 95% confidence interval, 1.3-7.2). These findings indicate that host, but not donor, MTHFR genotypes modify the risk of acute GVHD in recipients receiving MTX, in a manner consistent with our previously reported associations between MTHFR genotypes and MTX toxicity. A direct trade-off between drug toxicity and drug efficacy may play a role. Alternatively, the systemic folate environment, regulated by host tissues, might influence donor T-cell growth and activity.

Acute Disease↗

Norovirus genotypes causing gastroenteritis outbreaks in Finland 1998-2002.

BACKGROUND: Outbreak investigation methods for enteric viruses were improved in 1990s when gene amplification techniques were established in viral laboratories. OBJECTIVES: The objective of the study was to determine the causative agents for Finnish viral gastroenteritis outbreaks. Our aim was also to further characterise the norovirus strains, reveal the temporal occurrence of norovirus (NV) genotypes and to study some epidemiological aspects concerning the outbreaks. STUDY DESIGN: A total of 416 Finnish viral gastroenteritis outbreaks that occurred during 5 years (1998-2002), excluding those among hospitalised children, were investigated for enteric viruses. Stool samples were screened by electron microscopy as well as analyzed by specific noro- and astrovirus RT-PCR tests. Amplicon sequence analysis was used to find out norovirus genotypes. RESULTS: Noroviruses caused 252 (60.6%) of the outbreaks; other viruses, astro- or rotavirus, caused four epidemics. Norovirus epidemics occurred in all kinds of settings, most often in hospitals (30.6%) and in restaurants and canteens (14.3%). Both NV genogroups were found every year, but NV GGII outbreaks always outnumbered those of GGI. All but one outbreak at hospitals and nursing homes were of genotype GII. Polymerase sequence analysis revealed a variety of NV genotypes; six GI and at least eight GII genotypes. The GI.3 Birmingham-like and GII.4 Bristol-like genotype appeared every year, whereas the other types were circulating for shorter periods or sporadically. During the study period the genotypes GII.4 (Bristol), GII.1 (Hawaii), an emerging genotype GIIb, and a new variant of GII.4 predominated in that order. Indication for rapid genetic changes in the genotype GII.4 was also noticed. CONCLUSIONS: Noroviruses were the most prevalent causative agents in the outbreaks. Many NV genotypes were circulating, and a shift in the predominant genotypes was evident between epidemic seasons.

Caliciviridae Infections↗

Epidemiological study of hepatitis B virus genotypes, core promoter and precore mutations of chronic hepatitis B infection in Hong Kong.

BACKGROUND/AIMS: We conducted a population study to document the prevalence of hepatitis B virus (HBV) genotypes in Hong Kong. METHODS: HBV genotypes, core promoter (CP) and precore mutations were determined in 776 asymptomatic patients. RESULTS: 92.6% patients had single genotype [B (32.5%), C (62.5%)]. 99.1% of genotype B was subtype Ba. Patients with age <50 years had a lower prevalence of genotype B than patients with age >51 years (32.5% vs. 41%, respectively, P=0.028). Compared to patients with genotype C, patients with genotype B had a higher cumulative rate (P=0.018) and younger age (40.1 vs. 34.2 years, respectively, P=0.018) of HBeAg seroconversion. There were no differences in the HBV DNA levels between patients with genotypes B and C, and with wild-type and mutants of CP and precore regions. By multivariate analysis, patients with genotype C and with CP mutations had higher alanine aminotransferase (ALT) levels. CONCLUSIONS: B and C were the two most common HBV genotypes in Hong Kong. The former had a higher chance of earlier HBeAg seroconversion and lower ALT levels. The prevalence of genotype B was lower in patients with age <50, probably related to influx of immigrants from China since 1949.

Adolescent↗

Evaluation of a new assay for hepatitis C virus genotyping and viral load determination in patients with chronic hepatitis C.

A new method for hepatitis C virus (HCV) genotyping that analyzes products generated with the HCV Amplicor Monitor Test has been developed. One hundred and sixty-two Japanese patients with chronic hepatitis C, including 59 patients with hemophilia, were tested for HCV genotypes and viral loads with this new test, and the results were compared with those of a genotyping assay that involved direct sequencing of the E1 region. HCV genotypes and viral loads were also compared between patients with and without hemophilia. There were no discrepancies between the two methods in determining genotypes 2a, 2b, and 3a. However, two patients infected with 1a were mistyped as 1b with the new assay. One patient not classified by this assay was genotype 4. Genotypes found in patients without hemophilia were 1b, 2a, and 2b. Genotypes 1a, 3a, and 4, which were minor variants in Japan, were detected only in patients with hemophilia. In addition, J type, which is a subtype of 1b that originated in Japan, was found at low frequency in hemophiliacs. Thus, the HCV genotypes in patients with hemophilia are likely to be of foreign origin. Overall, this new assay was accurate except for genotype 1a and 4, and allowed simultaneous assessment of genotype and viral load.

Adult↗

'Hbe minus' mutants of hepatitis B virus. Molecular characterization and its relation to viral genotypes.

The precore-core and S genes of HBV were directly sequenced from serum samples of 42 patients with chronic hepatitis B (16 hepatitis Be antigen [HBeAg]+and 26 anti-HBe+). Viral genotype A was identified in 12 cases, genotype D in 11 and genotype F in 19 cases. Precore mutations, mainly M1 (G1896A, stop at codon 28) were similarly found among viral genotypes A and D: seven cases (58%) and six cases (55%), respectively. The selection of M1 mutants from genotype D resulted in a more stable encapsidation signal but was less stable for genotype A precore mutants. Oddly enough, the encapsidation signal of M1 precore mutants from genotype F sequences were evenly distributed among less stable (genotype A M1 mutants) and more stable encapsidation signal (genotype D M1 mutants). This study shows that the selection of precore mutants that preclude the HBeAg expression, including the M1 mutation, does not necessarily depend on the stabilization of the encapsidation signal or the viral genotype In addition, the particular behavior of genotype F genomes at precore region is described.

Adolescent↗

Apolipoprotein E genotypes and response of plasma lipids and progression-regression of coronary atherosclerosis to lipid-lowering drug therapy.

OBJECTIVES: We sought to examine the association of apolipoprotein (apo) E genotypes with baseline plasma lipid levels and severity of coronary artery disease (CAD), as well as the response to treatment with fluvastatin in the Lipoprotein and Coronary Atherosclerosis Study (LCAS). BACKGROUND: Apo E genotypes have been associated with plasma lipid levels and CAD. However, the influence of apo E genotypes on the response of plasma lipids and CAD progression or regression to statin treatment in patients with mildly to moderately elevated cholesterol remains unknown. METHODS: Apo E genotypes were determined by polymerase chain reaction and restriction mapping. Plasma lipids were measured at baseline and 12 weeks after therapy with fluvastatin or placebo in 320 subjects. In 287 subjects, quantitative coronary angiography was performed at baseline and after 2.5 years of treatment. RESULTS: Subjects with the 3/3 genotype had greater reductions in total cholesterol (20.4% vs. 15.4%, p = 0.01) and low density lipoprotein (LDL) cholesterol (28.8% vs. 22.7%, p = 0.03) than did the subjects with the 3/4 or 4/4 genotype. In contrast, subjects with the 2/3 genotype (n = 10) had a greater increase in high density lipoprotein cholesterol (19.1%) than did the subjects with the 3/3 genotype (4.3%, p = 0.002) and those with the 3/4 or 4/4 genotype (7.0%, p = 0.02). Subjects with the 3/4 or 4/4 genotype had an increased frequency of previous angioplasty, but other measures of baseline CAD severity and baseline lipids did not differ significantly among the genotypes, nor did CAD progression or clinical events. CONCLUSIONS: Although subjects with the epsilon4 allele had less reduction in LDL cholesterol with fluvastatin, they had similar benefit in terms of CAD progression.

Anticholesteremic Agents↗

HIV increases hepatitis C viraemia irrespective of the hepatitis C virus genotype.

In case of coinfection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV), HCV viraemia is increased. Because the HCV genotype 1 is associated with elevated viraemia, the increase in HCV viraemia observed and described in HIV+ patients could be attributed to the predominance of HCV genotype 1 in these patients. Therefore, the purpose of this study was to quantify HCV RNA in patients coinfected with HIV and HCV, according to the HCV genotype. The HCV genotype was thus determined in serum samples of 59 HIV+HCV+ patients and 51 HIV-HCV+ patients. HCV RNA was quantified using a branched DNA assay and the HCV genotype was determined using the "InnoLiPA" technique. The distribution of the HCV genotype was not significantly different in the two groups of patients, and there were even more patients infected by genotype 1 in the HIV-HCV+ group. The mean HCV viraemia of patients infected by HCV genotype 1 and by HCV genotype 3 was higher in patients coinfected by HIV than in HIV- patients (p < 10(-7) and p = 0.05, respectively). The increase in HCV viraemia observed in HIV+ patients was not the result of a specific distribution of HCV genotype in these patients. HIV infection was responsible for an increase in HCV viraemia irrespective of the HCV genotype.

Adult↗