The Hardy-Weinberg law1–4 presents a mathematical statement that describes the relationship between gene frequencies and genotype frequencies: gene frequencies at a locus in a randomly interbreeding diploid population and population genotype frequencies remain constant from generation to generation if mating is random and mutation, selection, and migration do not occur. The law states a fundamental principle of population genetics that is approximately true for small, and holds with increasing exactness for large populations. Should the frequencies be perturbed for any reason, they will come to the expected equilibrium frequencies after one generation of random mating.The Hardy-Weinberg law can be used for analytical purposes. It is suitable to test the hypothesis of panmixia and evolutionary stasis. Moreover, it represents a null hypothesis to test in genetic studies. However, according to our personal experience, data for Hardy-Weinberg equilibrium (HWE) calculations in studied populations are not always presented in articles with data on the genotype distributions of biallelic polymorphisms of Mendelian inheritance. In this retrospective survey, we tested in papers published in Gut , if this important and qualifying law was checked in studies investigating genetic polymorphisms between 1998 and April 2003.We collected genotype distributions published in papers in Gut from 1998 (volume 42) to 2003 (volume 52). Of 2389 total publications, we found 69 where genetic polymorphisms were part of the study. Of these, those articles that fulfilled the following criteria were selected: investigation of biallelic genetic polymorphism with Mendelian inheritance; use of healthy reference population in the study; and availability of genotype distribution data.We recalculated HWE in each paper and in each study group. For this purpose, we used Arlequin software (http://anthropologie.unige.ch/arlequin/).5,6 The level of statistical significance was set at p<0.05. Deviations from …

Background: Variants of the caspase activating recruitment domain 15/nucleotide oligomerisation domain 2 (CARD15/NOD2) gene have been associated with susceptibility to Crohn’s disease (CD). Aim: Our aim was to evaluate the allele frequencies of the CARD15 variants R702W, G908R, and 1007fs in Finnish inflammatory bowel disease (IBD) patients and to search for possible associations between CARD15 variants and occurrence of familial forms of IBD or complicated forms of CD. Patients and methods: We investigated 198 sporadic CD patients, 46 probands with familial CD, 27 CD probands from mixed IBD families, 99 unrelated patients with ulcerative colitis (UC), and 300 control individuals for the occurrence of the CARD15 gene variants R702W, G908R, and 1007fs. Results: In CD patients, the allele frequencies for the rare variants of these polymorphisms were 3.3%, 0.6%, and 4.8% (total 8.7%), and the corresponding frequencies in healthy controls were 1.8%, 0%, and 1.7% (total 3.5%) (8.7% v 3.5%; p<0.01). In UC patients allele frequencies were comparable with those in controls. The frequency of the 1007fs polymorphism variant allele was significantly higher among all CD patients than in controls (4.8% v 1.7%; p<0.01) but there was no significant difference in allele frequencies between the CD and UC groups. The 1007fs allele frequency was higher in familial CD than in non-familial cases with CD (10.9% v 3.5%; p<0.01). There were no significant differences in the allele frequencies of the R702W and G908R polymorphisms between CD patients, UC patients, and controls. We found that 15.5% of CD patients, 9.1% of UC patients, and 6.7% of controls carried at least one of the CARD15 variants. In CD patients carrying at least one of the three NOD2 variants, the ileum was affected more often than in non-carrier CD patients (90% v 73%; p<0.05), they had stricturing or penetrating disease more often than non-carriers (88% v 56%; p<0.01), and they had an increased need for bowel surgery. Conclusions: The frequency of NOD2 gene variants was lower in genetically homogenous Finns than in other populations. The 1007fs variant was associated with CD. The occurrence of CARD15 variants predicted ileal location as well as stricturing and penetrating forms of CD.

OBJECTIVES : To study the effect of weight loss and subsequent weight maintenance or weight regain on the activities of FVII and plasminogen activator inhibitor 1 (PAI-1) and the concentration of fibrinogen over 12 months in obese women consuming a hypoenergetic, low-fat diet with or without orlistat. In addition, the relation between the changes of the activities of PAI-1 and FVII with the changes of other cardiovascular risk factors were examined. METHODS AND PROCEDURES : Design—a 12-month randomized double-blind weight reduction trial of placebo and orlistat. Subjects—51 healthy obese women (age 44±0.7 y, BMI 36.2±0.5 kg/m 2 , mean±s.e.m.) Treatment—the participants were on a hypoenergetic diet (–600 kcal daily). The diet was adjusted for actual body weight (–300 kcal) at 6 months. Women were randomized to receive either orlistat 120 mg three times daily ( n =25) or placebo three times daily ( n =26) for 12 months according to a double-blind protocol after a 1 month run-in period. Measurements—changes of body weight, body composition, haemostatic and other cardiovascular risk factors were measured at 3–6 month intervals. The activity of plasma PAI-1 was measured by a chromogenic method, fibrinogen by the PT-derived method and the activity of FVII by the one-stage method. RESULTS : The changes in body weight between orlistat and placebo groups were not statistically significantly different. Orlistat did not influence haemostatic factors beyond its effect on weight loss. Therefore, the results of the orlistat and placebo groups were pooled. The average weight loss at 3, 6 and 12 months was 7.6, 9.5 and 10.0 kg, respectively ( P <0.001). Between 6 and 12 months, 35% of women regained weight, 24% had stable weight and 41% continued to lose weight. No changes in the mean plasma fibrinogen concentration were observed at any time point during the trial. During the first 3 months the activities of PAI-1 and FVII decreased. The decline depended on the magnitude of weight loss. Between months 6 and 12 the changes of PAI-1 and FVII activities paralleled the changes of body weight. The activities rose with weight rebound but remained below the 6-month values if weight loss was sustained or continued. The changes of serum insulin were significantly correlated with the changes of both PAI-1 and FVII at 6 months and with PAI-1 at 12 months. CONCLUSIONS : The maintenance of modest weight loss is associated with long-term benefits in PAI-1 and FVII in obese women. The change of serum insulin is associated with the changes of PAI-1 activities. Fibrinogen is not affected by modest weight loss.

The arginine/glutamine (Arg/Gln) polymorphism of the factor VII (FVII) gene is associated with variation in coagulation activity (FVII:C) and antigen concentration (FVII:Ag) of the FVII protein. We estimated frequency distributions of the Arg and Gln alleles and respective genotypes in North Karelia, and evaluated the utility of this polymorphism, serum lipids, and body mass index (BMI) in the prediction of the distributions of FVII:C and FVII:Ag in a cross-sectional study and in a prospective cohort study. The sample comprised 203 males and 262 females (aged 45-64 years) who were seen twice, in 1992 and 1995. The Arg/Arg genotype and the Arg allele frequencies were among the highest reported so far (86 and 93% respectively, in men; and 89 and 94% respectively, in women). Intragenotypic means of both FVII:C and FVII:Ag were significantly higher in the Arg/Arg genotype than in the Arg/Gln genotype in both genders. Also, intragenotypic variances were different in different genotypes in females. Regression relationships between the FVII:C and FVII:Ag and serum triglyceride, and total cholesterol levels and BMI were positive in both genotypes in both genders, which has not been found in other populations. In prospective analyses, average changes in the FVII:C and FVII:Ag were genotype specific in both genders, as were also regression relationships between these changes and changes in triglyceride level in females (P = 0.065 for FVII:C and P = 0.061 for FVII:Ag). A consequence of these complex genetic architectures is that predictive utility of the Arg/Gln genotypes depends on population, gender, serum lipid levels, and BMI, and changes in these factors over time.

Background: The majority of patients with inherited haemochromatosis carry two mutant alleles of the recently discovered HFE gene. Individuals heterozygous for the HFE mutation could be predisposed to end-stage liver disease due to other causes. Methods: The frequencies of the HFE gene mutations C282Y and H63D were determined in DNA samples obtained from 189 liver transplant patients and 225 healthy Finnish blood donors. Results: 5% of the 189 liver transplant recipients were heterozygotes and 0.5% homozygotes for the C282Y mutation, while 16% were heterozygotes and 0.5% homozygotes for the H63D mutation. These figures were not increased in comparison to controls, of whom 11% were C282Y heterozygotes, 16% H63D heterozygotes and 0.9% H63D homozygotes. Among recipients with acute non-A-E hepatitis (n = 31), the frequency of the H63D allele was higher than in controls (21% versus 9.1%, P < 0.01). Perls' stain for iron in explanted liver specimens was positive in 28% of recipients with alcoholic cirrhosis, 26% of patients with acute non-A-E hepatitis and 14% in the rest of the recipients. The HFE genotypes did not correlate with the iron status. Conclusion: Individuals heterozygous for either the C282Y or H63D mutation of the HFE gene are not at increased risk of developing chronic endstage liver disease. However, subjects heterozygous for the H63D mutation may have an increased risk to develop fulminant non-A-E hepatitis.

In the seventh national voluntary cross-sectional survey (in 1999) of Finnish patients with haemophilia A or B, type 3 von Willebrand disease or factor XIII deficiency, a plasma sample was received from 193 patients (67%). The samples were tested for hepatitis B and C, human immunodeficiency virus (HIV) and human T-cell leukaemia virus (HTLV) antibodies. Fifty-one percent of the patients were hepatitis C antibody positive and 34% hepatitis B core antibody positive. None of the patients had antibodies against HIV or HTLV. Eighteen percent of the patients had an elevated alanine aminotransferase activity. Abnormal alanine aminotransferase was significantly associated with hepatitis C seropositivity. No new seroconversions were detected among the haemophiliacs or patients with type 3 von Willebrand disease when compared with the last two surveys in 1993 and 1996, and there was no seroconversion in sole users of solvent/detergent-treated factor products. Currently, 32% of the patients use prophylactic factor treatment as their principal mode of therapy, particularly the younger patients with severe forms of the bleeding diseases.

The present study investigated the genetic basis for type II protein C deficiency in Finland, where this form has an unusually high incidence. We demonstrated that, first, a single novel mutation W380G in the protein C gene (PROC) explained 25/26 index patients, estimated to represent two thirds of all families with type II deficiency in Finland. Second, extended chromosomal conservation, i.e. a specific haplotype, around the W380G mutation was indicated in unrelated patients. Third, a local geographical origin for the W380G mutation was suggested by genealogical data. These results are in contrast to the heterogeneity in type II protein C deficiency elsewhere, but closely parallel disorders of the Finnish disease heritage. The high frequency of the type II disease can be explained by founder effect and subsequent enrichment of a single mutation in Finland. The present study also provided a simple means for genetic diagnosis of this disease and the genetic test can be included in the routine screenings in this population.

Finnish Red Cross Blood Transfusion Service, Department of Haemostasis, FIN-00310 Helsinki, Finland

TransfusionVolume 34, Issue 1 p. 85-86 Specificity and sensitivity of two second-generation enzyme-linked immunosorbent assays for antibodies to hepatitis C virus in blood donor screening Elina Kolho MD, Elina Kolho MD Finnish Red Cross Blood Transfusion Service Kivihaantie 7 00310 Helsinki, FinlandSearch for more papers by this authorRuth Naukkarinen MD, Ruth Naukkarinen MD Finnish Red Cross Blood Transfusion Service Kivihaantie 7 00310 Helsinki, FinlandSearch for more papers by this authorTom Krusius MD, Tom Krusius MD Finnish Red Cross Blood Transfusion Service Kivihaantie 7 00310 Helsinki, FinlandSearch for more papers by this author Elina Kolho MD, Elina Kolho MD Finnish Red Cross Blood Transfusion Service Kivihaantie 7 00310 Helsinki, FinlandSearch for more papers by this authorRuth Naukkarinen MD, Ruth Naukkarinen MD Finnish Red Cross Blood Transfusion Service Kivihaantie 7 00310 Helsinki, FinlandSearch for more papers by this authorTom Krusius MD, Tom Krusius MD Finnish Red Cross Blood Transfusion Service Kivihaantie 7 00310 Helsinki, FinlandSearch for more papers by this author First published: January 1994 https://doi.org/10.1046/j.1537-2995.1994.34194098615.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. References 1 Kolho E. Specificity and sensitivity of first and second generation anti-HCV ELISA in a low prevalence population. Transfus Med 1992; 2: 239– 42. 2 Kleinman S, Alter H, Busch M, et al. Increased detection of hepatitis C virus (HCV)-infected blood donors by a multiple-antigen HCV enzyme immunoassay. Transfusion 1992; 32: 805– 13. 3 Leon P, Lopez JA, Domingo C, Echevarria JM. Evaluation of laboratory assays for screening antibody to hepatitis C virus. Transfusion 1993; 33: 268– 70. 4 Hosein B, Fang CT, Popovsky MA, Ye J, Zhang M, Wang CY. Improved serodiagnosis of hepatitis C virus infection with synthetic peptide antigen from capsid protein. Proc Natl Acad SciUS A 1991; 88: 3647– 51. 5 Li XM, Reddy KR, Jeffers LJ, Parker T, de Medina M, Schiff ER. Indeterminate hepatitis C. Lancet 1993: 341: 835. Volume34, Issue1January 1994Pages 85-86 ReferencesRelatedInformation

The clinical significance of hepatitis C antibodies (anti-HCV) in a healthy population was studied by liver function tests and liver biopsies. The patient population consisted of 195 (96.1%) of the 203 blood donors found to be either anti-HCV positive or indeterminate by a recombinant immunoblot assay (RIBA) during the first year of anti-HCV screening of 307,606 donors in Finland using a first generation enzyme-linked immunosorbent assay. Alanine aminotransferase (ALT) levels in 67 donors reacting positively and in 128 reacting indeterminately by a second generation RIBA (RIBA-4) were monitored to evaluate the prevalence of liver damage. Serum N-terminal type III procollagen (PIIINP) concentrations were measured in all donors who fulfilled our criterion for possible hepatitis C (ALT values over two times the normal upper limit on two occasions or over five times the normal upper limit on one occasion) and in 23 randomly selected RIBA-4 positive donors without ALT abnormalities (control group). Two (1.6%) of the RIBA-4 indeterminate donors had ALT values compatible with possible hepatitis C (negative by polymerase chain reaction) whereas there were 25 (37.3%) such individuals among the RIBA-4 positive donors (P < 0.0005). Twenty (80%) of the latter 25 RIBA-4 positive donors with possible hepatitis C consented to liver biopsy. Of these 20 donors, 11 (55.0%) were found to have chronic persistent hepatitis, four (20.0%) mild, three (15.0%) moderate, and two (10.0%) severe chronic active hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

The frequency of infection with the six classified major genotypes of hepatitis C virus (HCV) was investigated in 447 infected volunteer blood donors from the following nine countries: Scotland, Finland, The Netherlands, Hungary, Australia, Egypt, Japan, Hong Kong, and Taiwan. Viral sequences in plasma from blood donors infected with HCV were amplified in the 5'-noncoding region and were typed by restriction fragment length polymorphism analysis. Electrophoresis of DNA fragments produced by cleavage with HaeIII-RsaI and ScrFI-HinfI allowed HCV types 1 (or 5), 2, 3, 4, and 6 to be identified. Further analysis with MvaI-HinfI allowed sequences of the type 5 genotype to be distinguished from sequences of the type 1 genotype. Types 1, 2, and 3 accounted for almost all infections in donors from Scotland, Finland, The Netherlands, and Australia. Types 2 and 3 were not found in the eastern European country (Hungary), where all but one of the donors were infected with type 1. Donors from Japan and Taiwan were infected only with type 1 or 2, while types 1, 2, and 6 were found in those from Hong Kong. HCV infection among Egyptians was almost always by type 4. Donors infected with HCV type 1 showed broad serological reactivity with all four antigens of the second generation Chiron RIBA-2 assay (Chiron Corporation, Emeryville, Calif.), while infection with divergent HCV genotypes elicited antibodies mainly reactive to c22-3 and c33c. Reactivities with antibodies 5-1-1 and c100-3 were infrequent and were generally weak, irrespective of the geographical origin of the donor. Because the envelope region of HCV is even more variable than the NS-4 region, it is likely that vaccines based on these proteins need to be multivalent and perhaps specifically adapted for different geographical regions.

The prevalence of hepatitis C antibodies (anti-HCV) among multitransfused patients was studied and compared with predicted values obtained from a post-transfusion hepatitis study and from data on the prevalence of anti-HCV among blood donors. The prevalence of hepatitis B core antibodies (anti-HBc) was also studied to determine the routes of transmission of hepatitis C virus. The patients consisted of 65 dialysis patients (57 on haemodialysis and 8 on continuous ambulatory peritoneal dialysis) and 71 leukaemia patients in long-term remission [49 with acute myeloid leukaemia (AML) and 22 with acute lymphatic leukaemia (ALL)]. The presence of anti-HCV was investigated using a second generation enzyme-linked immunosorbent assay. Reactive samples were confirmed by a second generation recombinant immunoblot assay. Anti-HBc was studied in the 65 dialysis patients and in 40 of the leukaemia patients. Three (4.6%) of the 65 dialysis patients and 12 (24.5%) of the 49 AML patients were anti-HCV positive whereas all of the ALL patients were seronegative. The total number of blood units transfused to 134 patients (data on two dialysis patients were not available) was 18,148, out of which 17,575 units had been transfused prior to the initiation of anti-HCV screening of blood donors. On the basis of the anti-HCV prevalence among blood donors and the incidence of post-transfusion hepatitis, the predicted number of seropositive patients was 11 and 18, respectively. Five of the 65 dialysis patients were anti-HBc positive, compared with only one of the 40 leukaemia patients.(ABSTRACT TRUNCATED AT 250 WORDS)

A retrospective study was carried out on the recipients of 73 units of blood from 53 donors found reactive for anti-HCV. The donors were screened with anti-HCV enzyme-linked immunosorbent assay (ELISA C-100) and reactivity was confirmed with the first generation recombinant immunoblot assay (RIBA I). Fifty-two patients were recipients of blood from donors reacting as RIBA I 'indeterminate' and 21 of blood from RIBA I 'positive' donors. Only three recipients (5.8%) from 'indeterminate' donors were anti-HCV positive indicating that such donors are very seldom infectious. Eleven (52.4%) recipients from 'positive' donors had antibodies to HCV, indicating that not all RIBA-positive donors are necessarily infectious. Pretransfusion samples of the seropositive recipients were unavailable. All samples were analyzed with the first generation ELISA and with either the second-generation ELISA or RIBA (RIBA II) in order to evaluate test sensitivity. RIBA II was more sensitive than RIB I. One RIBA I indeterminate donor was positive by RIBA II. His recipient had antibodies to HCV. Twelve RIBA I indeterminate and three RIBA I positive donors were negative by RIBA II. All their recipients were anti-HCV negative. The second-generation ELISA was also shown to be more sensitive than ELISA C-100. The second-generation ELISA detected six confirmed anti-HCV positive recipients who were negative by ELISA C-100.

Vox SanguinisVolume 63, Issue 2 p. 158-160 Specificity and Sensitivity of Two Second-Generation ELISA Tests in Detecting Hepatitis C Antibodies in Blood Donors Known to Be Reactive with a Supplemental Assay E. Kolho, Corresponding Author E. Kolho Finnish Red Cross Blood Transfusion Service Helsinki, FinlandFinnish Red Cross Blood Transfusion Service Kivihaantie 7 SF-00310 Helsinki (Finland)Search for more papers by this authorR. Naukkarinen, R. Naukkarinen Finnish Red Cross Blood Transfusion Service Helsinki, FinlandSearch for more papers by this authorT. Krusius, T. Krusius Finnish Red Cross Blood Transfusion Service Helsinki, FinlandSearch for more papers by this author E. Kolho, Corresponding Author E. Kolho Finnish Red Cross Blood Transfusion Service Helsinki, FinlandFinnish Red Cross Blood Transfusion Service Kivihaantie 7 SF-00310 Helsinki (Finland)Search for more papers by this authorR. Naukkarinen, R. Naukkarinen Finnish Red Cross Blood Transfusion Service Helsinki, FinlandSearch for more papers by this authorT. Krusius, T. Krusius Finnish Red Cross Blood Transfusion Service Helsinki, FinlandSearch for more papers by this author First published: September 1992 https://doi.org/10.1111/j.1423-0410.1992.tb02506.xCitations: 3AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume63, Issue2September 1992Pages 158-160 RelatedInformation

British Journal of HaematologyVolume 82, Issue 4 p. 781-782 ABOUT FAMILIAL DEFECTIVE RELEASE OF t-PA Jari Petäjä, Jari Petäjä Finnish Student Health Service, Töölönkatu 37 A, 00260 HelsinkiSearch for more papers by this authorTom Krusius, Tom Krusius Finnish Student Health Service, Töölönkatu 37 A, 00260 HelsinkiSearch for more papers by this authorDan Apter, Dan Apter Finnish Student Health Service, Töölönkatu 37 A, 00260 HelsinkiSearch for more papers by this authorTomi Koski, Tomi Koski Finnish Student Health Service, Töölönkatu 37 A, 00260 HelsinkiSearch for more papers by this author Jari Petäjä, Jari Petäjä Finnish Student Health Service, Töölönkatu 37 A, 00260 HelsinkiSearch for more papers by this authorTom Krusius, Tom Krusius Finnish Student Health Service, Töölönkatu 37 A, 00260 HelsinkiSearch for more papers by this authorDan Apter, Dan Apter Finnish Student Health Service, Töölönkatu 37 A, 00260 HelsinkiSearch for more papers by this authorTomi Koski, Tomi Koski Finnish Student Health Service, Töölönkatu 37 A, 00260 HelsinkiSearch for more papers by this author First published: December 1992 https://doi.org/10.1111/j.1365-2141.1992.tb06966.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References Petäjä, J., Rasi, V., Vahtera, E. & Myliyä, G. (1991) Familial clustering of defective release of t-PA. British Journal of Haematology. 79, 291 – 295. Volume82, Issue4December 1992Pages 781-782 ReferencesRelatedInformation

Sexual transmission of hepatitis C virus (HCV) was studied in 30 partners to anti-HCV positive multitransfused patients with a bleeding disorder. Anti-HCV ELISA C-100 was used as a screening test. Positive results were confirmed with the first generation RIBA test. Indeterminate samples were tested also with the second generation RIBA to verify the positivity. The time of sexual exposure added up was at least 95 years. 29 partners were anti-HCV seronegative. Only 1 partner was anti-HCV indeterminate. Thus sexual transmission of HCV was a rare event.