Genetic epidemiology of lipoprotein lipase deficiency in Saguenay-Lac-St-Jean (Québec, Canada).

Familial hyperchylomicronemia due to the lipoprotein lipase (LPL) activity deficiency (Type I hyperlipoproteinemia) is an autosomal recessive disorder with a prevalence estimated at one case per million. Thirty-four type I individuals are known in Saguenay-Lac-St-Jean (SLSJ), a geographically isolated region of Quebec. The prevalence of type I and LPL deficient heterozygote in this region was estimated at 1/6382 and 1/46 inhabitants respectively. The mean inbreeding coefficient was slightly elevated in the type I group compared with three control groups. The mean kinship coefficient was 15.1 times higher in the type I group than in the control groups. The high prevalence of type I in SLSJ appears to be the result of the emigration of carriers of LPL deficiency from Charlevoix, another isolated region of quebec to the SLSJ region. Endogamy also played a crucial role in increasing the prevalence of type I in SLSJ.     

Genetic epidemiology of sensorimotor polyneuropathy with or without agenesis of the corpus callosum in northeastern Quebec

Sensorimotor polyneuropathy with or without agenesis of the corpus callosum (McKusick number 218000) is a disorder that has a high frequency in Saguenay-Lac-St-Jean (SLSJ), a geographically isolated region of northeastern Quebec. The incidence at birth and the carrier rate were estimated, respectively, at 1/2117 liveborns and 1/23 inhabitants. Remote consanguinity was found in several polyneuropathic families while the mean kinship coefficient was 2.7 times higher in the polyneuropathic group than in control groups. The birth places of the individuals with sensorimotor polyneuropathy and their parents did not show a clustered nonuniform distribution. The genealogical reconstruction suggests that the high incidence of polyneuropathy in SLSJ is likely to be the result of a founder effect. It also suggests that a unique mutation accounts for most, if not all, of the cases of sensorimotor polyneuropathy known in this region.     

Population genetics of hereditary hemochromatosis in Saguenay Lac-Saint-Jean (Quebec, Canada).

Hereditary hemochromatosis (HH) is an autosomal recessive disorder that has a high prevalence in Caucasian populations. Based on HLA typing in 18 families, the gene frequency was estimated 0.12. The homozygote frequency was 0.014 and the heterozygote frequency was 0.21 in Saguenay Lac-Saint-Jean (SLSJ), a geographically isolated region of northeastern Quebec. The genealogical reconstruction showed that 15 of the 57 obligate carriers of the HH gene could be traced back to a unique ancestor in the 18th century. The mean coefficients of inbreeding and kinship were 17 and 15 times, respectively, higher in the HH group than in three control groups. The values of both coefficients were much higher than those found in other HH populations and in most of the other recessive disorders prevalent in SLSJ.     

Clinical, metabolic, and genetic aspects of cytochrome C oxidase deficiency in Saguenay-Lac-Saint-Jean.

Thirty-four children with lactic acidosis and Leigh encephalopathy due to cytochrome C oxidase (COX) deficiency distributed in 28 families have recently been identified in northeastern Quebec, particularly in the Saguenay-Lac-Saint-Jean (SLSJ) region. The segregation analysis was consistent with an autosomal recessive mode of inheritance. The incidence was estimated at 1/2,063 live births between 1979 and 1990, and the carrier rate was estimated at 1/23 inhabitants in SLSJ. In SLSJ, the places of origin of the COX-deficient children and their parents did not show a clustered nonuniform distribution. The genealogical reconstruction of 54 obligate carriers identified 26 ancestors common to all of them. Twenty-two were 17th-century Europeans, suggesting that the COX-deficient gene was introduced in the French-Canadian population by early settlers. These results support the hypothesis of a founder effect for COX deficiency in northeastern Quebec. Clinical findings are reported for 15 of these COX-deficient patients, age 6 mo to 11 years. Moderate developmental delay, hypotonia, ataxia, strabismus, and mild facial dysmorphism were frequent. Eleven children died in episodes of fulminant metabolic acidosis. The patients had elevated blood and cerebrospinal fluid lactate levels, decreased blood bicarbonate levels, and normal blood pH. Leigh disease and microvesicular steatosis of the liver were present in all affected patients for whom postmortem examination was performed. This biochemically uniform group of patients showed a wide range of clinical severity.     

Inbreeding in Saguenay-Lac-St-Jean (Quebec, Canada): a study of Catholic Church dispensations 1842-1971.

Saguenay-Lac-St-Jean (SLSJ) is a rather geographically isolated region of Quebec which shows a high occurrence of hereditary disorders. It has been suggested that high inbreeding might explain this situation. We studied the inbreeding in the SLSJ region by 10-year periods from 1842 till 1971 using the Catholic Church dispensations. The values of the mean inbreeding coefficient were found to be low during the whole period, reaching a peak of 22.94 x 10(-4) during the period 1902-1911. The values observed in the SLSJ were lower than those found in most regions of Quebec and similar to those reported in European populations.     

Fertility in couples heterozygous for the tyrosinemia gene in Saguenay Lac-St-Jean

A case-control study of 84 couples from Saguenay-Lac-St-Jean, jointly heterozygous for the tyrosinemia gene, was done to determine whether the birth of an homozygous child affected their fertility rates. The mean number of children born to tyrosinemia and control couples between 1940 and 1986 was not different (p greater than 0.05). The knowledge that tyrosinemia was an autosomal recessive disorder, with risk of recurrence in these families, did not appear to modify reproductive behaviour. Fertility fell significantly in both the tyrosinemia and control families in the period of observation. This change reflects the decline in fertility of French Canadians in general during this period.     

Different molecular basis for fumarylacetoacetate hydrolase deficiency in the two clinical forms of hereditary tyrosinemia (type I).

Hereditary tyrosinemia is characterized by a deficiency of the enzyme fumarylacetoacetate hydrolase (FAH; E.C.3.7.1.2), the last enzyme in the catabolic pathway of tyrosine. FAH was purified from rat and human liver and was used to immunize rabbits. Specific antibodies were used to probe protein extracts of livers and other tissues of normal and tyrosinemic patients. No immunoreactive FAH band was observed on immunoblots of liver, kidneys, and lymphocytes from patients presenting with the acute form of hereditary tyrosinemia. Patients with the chronic form had immunoreactive FAH at a level approximately 20% of normal liver values, which was correlated with the measured enzymatic activity. Immunoblot analysis of aborted fetal tissues revealed normal FAH immunoreactivity in normal liver and kidneys. No FAH immunoreactivity was found in liver and kidneys of tyrosinemic fetuses. The presence of FAH immunoreactivity in normal fetal tissues suggests that deficient FAH activity in tyrosinemia is not simply related to a developmentally regulated expression of the enzyme. By this immunoblot assay, FAH was detected in most human tissues, with maximal immunoreactivity in liver and kidneys and with only trace amounts in chorionic villi and cultured amniocytes. These data confirm that the primary defect in the acute form of hereditary tyrosinemia is an absence of FAH. Moreover, these data suggest that both clinical forms of the disease have a different molecular basis.     

A genomewide linkage-disequilibrium scan localizes the Saguenay-Lac-Saint-Jean cytochrome oxidase deficiency to 2p16

Leigh syndrome (LS) affects 1/40,000 newborn infants in the worldwide population and is characterized by the presence of developmental delay and lactic acidosis and by a mean life expectancy variously estimated at 3-5 years. Saguenay-Lac-Saint-Jean (SLSJ) cytochrome oxidase (COX) deficiency (LS French-Canadian type [LSFC] [MIM 220111]), an autosomal recessive form of congenital lactic acidosis, presents with developmental delay and hypotonia. It is an LS variant that is found in a geographically isolated region of Quebec and that occurs in 1/2,178 live births. Patients with LSFC show a phenotype similar to that of patients with LS, but the two groups differ in clinical presentation. We studied DNA samples from 14 patients with LSFC and from their parents, representing a total of 13 families. Because of founder effects in the SLSJ region, considerable linkage disequilibrium (LD) was expected to surround the LSFC mutation. We therefore performed a genomewide screen for LD, using 290 autosomal microsatellite markers. A single marker, D2S1356, located on 2p16, showed significant (P < 10(-5)) genomewide LD. Using high-resolution genetic mapping with additional markers and four additional families with LSFC, we were able to identify a common ancestral haplotype and to limit the critical region to approximately 2 cM between D2S119 and D2S2174. COX7AR, a gene encoding a COX7a-related protein, had previously been mapped to this region. We determined the genomic structure and resequenced this gene in patients with LSFC and in controls but found no functional mutations. Although the LSFC gene remains to be elucidated, the present study demonstrates the feasibility of using a genomewide LD strategy to localize the critical region for a rare genetic disease in a founder population.     

Anatomy of a founder effect: myotonic dystrophy in Northeastern Quebec

Founder effects are largely responsible for changes in frequency profiles of genetic variants in local populations or isolates. They are often recognized by elevated incidence of certain hereditary disorders as observed in regions of Charlevoix and Saguenay-Lac-Saint-Jean (SLSJ) in Northeastern Quebec. Dominantly transmitted myotonic dystrophy (DM1) is highly prevalent in SLSJ where its carrier rate reaches 1/550, compared with 1/5,000 to 1/50,000 elsewhere. To shed light on the origin of DM1 in this region, we have screened 50 nuclear DM1 families from SLSJ and studied the genetic variation in a 2.05 Mb (2.9 cM) segment spanning the site of the expansion mutation. The markers analyzed included 22 biallelic SNPs and two microsatellites. Among 50 independent DM1 chromosomes, we distinguished ten DM1-associated haplotypes and grouped them into three haplotype families, A, B and C, based on the relevant extent of allele sharing between them. To test whether the data were consistent with a single entry of the mutation into SLSJ, we evaluated the age of the founder effect from the proportion of recombinant haplotypes. Taking the prevalent haplotype A1_21 (58%) as ancestral to all the disease-associated haplotypes in this study, the estimated age of the founder effect was 19 generations, long predating the colonization of Nouvelle-France. In contrast, considering A1_21 as ancestral to the haplotype family A only, yielded the estimated founder age of nine generations, consistent with the settlement of Charlevoix at the turn of 17th century and subsequent colonization of SLSJ. We conclude that it was the carrier of haplotype A (present day carrier rate of 1/730) that was a driver of the founder effect, while minor haplotypes B and C, with corresponding carrier rates of 1/3,000 and 1/10,000, respectively, contribute DM1 to the incidence level known in other populations. Other studies confirm that this might be a general scenario in which a major driver mutation/haplotype issued from a founder effect is found accompanied by distinct minor mutations/haplotypes occurring at background population frequencies.Electronic Supplementary Material Supplementary material is available for this article at     

Variability of human hepatic UDP-glucuronosyltransferase activity.

The availability of a unique series of liver samples from human subjects, both control patients (9) and those with liver disease (6; biliary atresia (2), retransplant, chronic tyrosinemia type I, tyrosinemia, Wilson's disease) allowed us to characterize human hepatic UDP-glucuronosyltransferases using photoaffinity labeling, immunoblotting and enzymatic assays. There was wide inter-individual variation in photoincorporation of the photoaffinity analogs, [32P]5-azido-UDP-glucuronic acid and [32P]5-azido-UDP-glucose and enzymatic glucuronidation of substrates specific to the two subfamilies of UDP-glucuronosyltransferases. However, the largest differences were between subjects with liver disease. Glucuronidation activities toward one substrate from each of the UDP-glucuronosyltransferases subfamilies, 1A and 2B, for control and liver disease, respectively, were 1.7-4.5 vs 0.4-4.7 nmol/mg x min for hyodeoxycholic acid (2B substrate) and 9.2-27.9 vs 8.1-75 nmol/mg x min for pchloro-m-xylenol (1A substrate). Microsomes from a patient with chronic tyrosinemia (HL32) photoincorporated [32P]5-azido-UDP-glucuronic acid at a level 1.5 times higher than the other samples, was intensely photolabeled by [32P]5-azido-UDP-glucose and had significantly higher enzymatic activity toward p-chloro-m-xylenol. Immunoblot analysis using anti-UDP-glucuronosyltransferase antibodies demonstrated wide inter-individual variations in UDP-glucuronosyltransferase protein with increased UDP-glucuronosyltransferase protein in HL32 microsomes, corresponding to one of the bands photolabeled by both probes. Detailed investigation of substrate specificity, using substrates representative of both the 1A (bilirubin, 4-nitrophenol) and 2B (androsterone, testosterone) families was carried out with HL32, HL38 (age and sex matched control) and HL18 (older control). Strikingly increased (5-8-fold) glucuronidation activity was seen in comparison to HL18 only with the phenolic substrates. The results indicate that one or more phenol-specific UDP-glucuronosyltransferase 1A isoforms are expressed at above normal levels in this tyrosinemic subject.     

Hereditary disorders in Saguenay-Lac-St-Jean (Quebec, Canada)

Saguenay-Lac-St-Jean is a geographically isolated region located in northeastern Quebec. Opened to the white settlement in 1938, its immigrants mainly came from Charlevoix, another isolated region of Quebec. The prevalence and/or incidence of several autosomal dominant and recessive disorders are very high. The overall birth prevalence of the recessive disorders was calculated at 1/207 living births and the overall carrier rate at 1/7 inhabitants. This situation may be explained by migration and social factors.     

Location score and haplotype analyses of the locus for autosomal recessive spastic ataxia of Charlevoix-Saguenay, in chromosome region 13q11

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a clinically homogeneous form of early-onset familial spastic ataxia with prominent myelinated retinal nerve fibers. More than 300 patients have been identified, and most of their families originated in the Charlevoix-Saguenay region of northeastern Quebec, where the carrier prevalence has been estimated to be 1/22. Consistent with the hypothesis of a founder effect, we observed excess shared homozygosity at 13q11, among patients in a genomewide scan of 12 families. Analysis of 19 pedigrees demonstrated very tight linkage between the ARSACS locus and an intragenic polymorphism of the gamma-sarcoglycan (SGCG) gene, but genomic DNA sequence analysis of all eight exons of SGCG revealed no disease-causing mutation. On the basis of haplotypes composed of seven marker loci that spanned 11.1 cM, the most likely position of the ARSACS locus was 0.42 cM distal to the SGCG polymorphism. Two groups of ARSACS-associated haplotypes were identified: a large group that carries a common SGCG allele and a small group that carries a rare SGCG allele. The haplotype groups do not appear to be closely related. Therefore, although chromosomes within each haplotype group may harbor a single ARSACS mutation identical by descent, the two mutations could have independent origins.     

The problem of the transgeneration phenomenon of genome instability in sick children of different age groups after the accident at the Chernobyl Nuclear Power Plant

A complex genetic examination of children which belong to two cohorts and their parents were carried out. The first cohort included children and constantly living on territories contaminated with radionuclides (Novozybkov district, Bryansk region). They were subdivided in groups according to the ontogenetic age periods of development of their parents at the time of the Chernobyl accident. In the children born in 1986-1995 the level of aberrant genomes is significantly higher as compared to the control (p < 0.001). In children born in 1998-2002 the differences are insignificant (p > 0.05). The frequency of aberrant genomes had a tendency to decrease with the period of time between the birth date of a child and the moment of the accident. Analysis of the results of cytogenetic investigation for the same living on territories with different densities of radioactive contamination (zone I-- 627-688 kBq/m2, 137Cs and zone II-- 135-402 kBq/m2, 137Cs) revealed insignificant differences in the spectrum and average frequencies of chromosome aberrations. The second cohort included children born in 1987-1991 and 1993-2002 from irradiated fathers (Chernobyl clean-up workers) and unirradiated mothers living on territories without radionuclide contamination. These children also displayed increased frequencies of aberrant genomes as compared to the control (p < 0.001). The analysis of the dynamics years of birth of cytogenetic disturbances in the same cohorts of children showed the average frequencies of aberrant genomes remain higher than the control level. In most of the children of both cohorts the repair synthesis of genome DNA by gamma- and UV-radiation is reduced as compared to one in the children from the control group.     

Ethnic distribution of phenylketonuria in the north German population

Summary Results of neonatal screening for phenylketonuria (PKU) suggest a west-east gradient of PKU gene frequency in central Europe. In order to test the hypothesis that the unexpectedly high prevalence of PKU in northwestern Germany (northern region of the FRG) is due to the migration of Germans from eastern regions of prewar Germany in the decade after World War II. grandparental origin was determined in a group of 87 pediatric PKU patients and in a control group of 210 children. Grandparents of east German origin were significantly more frequent among the PKU patients. The observed frequency distribution of grandparental subgroups was described by a theoretical distribution in order to obtain a likely set of values for the ratio between the frequency of the PKU gene in the autochthonous populations of prewar northeastern and northwestern Germany. The most likely value for the PKU gene frequency ratio was 1.37, which indicates that the prevalence for PKU in prewar northeastern Germany was almost twice as high as in the autochthonous population of the northwest.Dedicated to Professor P. E. Becker on the occasion of his 75th birthday     

Feasibility of chemical screening of urine for neuroblastoma case finding in infancy in Quebec.

Neuroblastoma is the most common fatal solid tumour of childhood. Studies in Japan suggest that screening urine at 6 months for tumour-derived metabolites greatly improves early case finding and prognosis. The incidence rate of neuroblastoma in Quebec is at least 1 per 10,330 live births, higher than that of all other diseases responding to early treatment except congenital hypothyroidism screened for in the Quebec Network of Genetic Medicine. The feasibility of chemical screening of urine for elevated levels of homovanillic acid and vanillylmandelic acid in Quebec was assessed. The cost-effectiveness of screening 100,000 infants per year would be high (cost-benefit ratio 2.4), with a net saving of about $280,000 and eight lives per year. The estimated cost of adding neuroblastoma screening to the existing urine metabolite screening program is $70,700. The apparent sensitivity of the proposed test is 0.859 and the rate of false-positive results about 0.1%, both acceptable values. The attitude of potential participants toward the present urine screening program and the addition of a "tumour test" was positive. The results indicate that a pilot study of neuroblastoma screening in Quebec could be undertaken.     

The accident at Chernobyl and outcome of pregnancy in Finland.

OBJECTIVE--To evaluate the outcome of pregnancy in Finnish women after the accident at the Chernobyl nuclear power plant on 26 April 1986. DESIGN--Geographic and temporal cohort study. SETTING--Finland divided into three zones according to amount of radioactive fallout. SUBJECTS--All children who were exposed to radiation during their fetal development. Children born before any effects of the accident could be postulated--that is, between 1 January 1984 and 30 June 1986--served as controls. INTERVENTIONS--Children were divided into three temporal groups: controls, children who were expected to be born in August to December 1986, and children who were expected to be born in February to December 1987. They were also divided, separately, into three groups according to the three geographic zones. END POINT--Incidence of congenital malformations, preterm births, and perinatal deaths. MEASUREMENTS AND MAIN RESULTS--There were no significant differences in the incidence of malformations or perinatal deaths among the three temporal and three geographic groups. A significant increase in preterm births occurred among children who were exposed to radiation during the first trimester whose mothers lived in zones 2 and 3, where the external dose rate and estimated surface activity of caesium-137 were highest. CONCLUSIONS--The results suggest that the amount of radioactive fallout that Finnish people were exposed to after the accident at Chernobyl was not high enough to cause fetal damage in children born at term. The higher incidence of premature births among malformed children in the most heavily polluted areas, however, remains unexplained.     

Operation of natural selection on human height

An association between fertility, sibship size, and mid-parental height was analyzed in an endemic rural population of Lahore, Punjab, Pakistan. The study was carried out on the population of Muridke, a town 27 km north of Lahore. Families were visited to record the heights of father and mother, total number of siblings born in each family, and sex of children. The data were analyzed for fertility and mean sibship size in relation to: maternal height (the data are based on 827 siblings consisting of 3337 total siblings born out of which 2870 were alive); paternal height (the data consist of a sample of 860 siblings containing 3420 total siblings out of which 3000 were alive); and mid-parental height (the data are comprised of 790 siblings composed of 3122 total siblings born of which 2693 were alive). The data were analyzed in 3 ways, i.e., fertility and mean sibship size in relation to maternal height, paternal height, and mid-parental height. The maternal heights were arranged into 6 classes. Mean maternal height in the sample if 152.59 +or- 4.48 cm, that of father 164.94 +or- 4.59 cm, and for mid-parental heights the mean is 159.65 +or- 6.00 cm. The highest mean number of total siblings born was not associated with the mean value class, 152-153, rather it was observed in the next higher class, 154-155. The lowest coefficient of variation was seen in the mean value class, though not the variance. If the average range classes, 3 + 4, are combined, this shows higher mean number of total siblings born than the remaining classes, and also the coefficient of variation is the lowest. For paternal heights, the mean value class, 164-165 shows less mean number of children than the next higher class, 166-167. When the average range classes, 4 + 5, are combined together, a higher mean number of total siblings is observed compared with the remaining classes. For mid-parental heights, in the mean value class, 158-159, mean number of total siblings born are more than the other classes. The analysis of the combined average range classes (3 + 4) shows higher mean sibship size compared with the remaining classes.     

Postnatal effects in children irradiated during the intra-uterine development, as a result of failure at the Chernobyl NPP

Somatic and genetic effects at children who have undergone the influence of ionizing radiation during in utero development and at the subsequent stages ontogenesis are investigated, in view of dozes of the general irradiation and equivalent dozes of an irradiation of red bone brain. 1144 children were examined: 1st group consisted of children who have been born from women pregnant at the moment of failure, evacuated from Pripyat; 2nd group included children who have been born from women pregnant at the moment of failure, stayed to live in a zone of the strict radiation control; 3rd group was the control group--children who have been born in 1986, living in safe region of the Ukraine according to radiation conditions. The presence of direct correlation link between quantity of small anomalies of the development and the total radiation dose of the fetus (R = 0.61, p < 0.002) and inverse link with fetus age at the moment of radiation factor effect (R = -0.53, p < 0.003) has been established. Significant correlation links between the total radiation dose and the level of children health (R = 0.45, p < 0.03); the equivalent radiation dose of the red bone marrow and the frequency of damages in the chromosomal apparatus of the somatic cells (1st group--R = 0.51, p < 0.02; 2nd group--R = 0.62, p < 0.002) have been revealed.     

Weight growth in infants born to mothers who smoked during pregnancy.

OBJECTIVE--To determine whether maternal smoking during pregnancy causes impairment in growth after birth. DESIGN--Longitudinal study. SETTING--Six medical university centres of six towns of north, central, and south Italy. SUBJECTS--12,987 babies (10,238 born from non-smoking mothers, 2276 from mothers smoking one to nine cigarettes a day, and 473 from mothers smoking > or = 10 cigarettes a day) entered the study. MAIN OUTCOME MEASURES--Difference in weight gain between children born to smoking mothers and those born to non-smoking mothers. Weight was measured at birth and at 3 and 6 months of age. Maternal smoking habit was derived from interview on third or fourth day after delivery. RESULTS--Compared with children born to mothers who did not smoke during pregnancy, the birth weights of children born to mothers who smoked up to nine cigarettes a day were 88 g (girls) and 107 g (boys) lower; in children born to mothers who smoked > or = 10 cigarettes a day weights were 168 g and 247 g lower. At six months of age for the first group the mean weight for girls was 9 g (95% confidence interval -47 g to 65 g) higher and for boys 64 g (-118 g to -10 g) lower than that of children born to mothers who did not smoke. The corresponding figures for the second group were 28 g (-141 g to 85 g) lower for girls and 24 g (-136 g to 88 g) lower for boys. CONCLUSIONS--The deficits of weight at birth in children born to mothers who smoked during pregnancy are overcome by 6 months of age. These deficits are probably not permanent when smoking habit during pregnancy is not associated with other unfavourable variables (such as lower socioeconomic class).     

HIV infection among women undergoing abortion in Montreal.

OBJECTIVE: To determine the seroprevalence and correlates of HIV infection in a subpopulation of women of childbearing age in Montreal. DESIGN: Anonymous unlinked seroprevalence study. SETTING: Pregnancy termination unit in a teaching hospital in Montreal. PARTICIPANTS: Women presenting for abortion from July 1989 to June 1993 who resided in Quebec and were not known to have HIV infection; 12,017 (99.6%) of 12,068 eligible women were included in the study. INTERVENTION: HIV antibody testing of serum left over from samples obtained for routine Rh typing; the same algorithm as for serodiagnostic testing, namely enzyme immunoassay (EIA) followed by confirmatory testing of repeatedly EIA-reactive samples, was used. OUTCOME MEASURES: HIV serostatus by age, marital status, region of residence (metropolitan Montreal versus other), country of birth and number of living children. RESULTS: Most (84.7%) of the subjects resided in metropolitan Montreal. The median age was 27.0 (range 13 to 50) years. The serum samples of 22 women were confirmed to be HIV positive, for an overall seroprevalence rate of 1.8 per 1000 (95% confidence interval 1.1 to 2.8). The seroprevalence rate did not vary significantly by age, marital status, region of residence or study year. However, it was strongly correlated with country of birth: Canada 0.16, Haiti 23.5, HIV-endemic countries other than Haiti 5.3 and non-HIV-endemic countries other than Canada 0.0 per 1000. The seroprevalence rate among women born in Haiti was 147 times higher than that among women born in Canada (p < 0.0001). Of the women born in Haiti the rate was 3.0 times greater among those who immigrated to Canada in 1985 or later than among those who immigrated earlier (p = 0.047). CONCLUSIONS: The results of this study indicate that the HIV seroprevalence rate among women in Montreal is strongly associated with country of birth, women born in HIV-endemic countries, especially Haiti, having the highest rate. These results will help in the development of policies regarding HIV antibody testing and prevention of HIV transmission in Quebec.