Genetic epidemiology of hereditary tyrosinemia in Quebec and in Saguenay-Lac-St-Jean.

Hereditary tyrosinemia type I is an autosomal recessive disorder that was recognized in Saguenay-Lac-St-Jean (SLSJ) (Quebec) in 1967. Ninety-eight tyrosinemic children, including some of the 113 children born in the SLSJ region, have been screened by the Quebec Network of Genetic Medicine in the whole province since 1970. The geographical distribution of the 98 children screened showed the majority of them to have been born in the northeastern part of Quebec. The prevalence at birth was estimated at 1/1,846 live borns, and the carrier rate was estimated at 1/20 inhabitants in the SLSJ region. Three control groups matched to the tyrosinemic obligate-carrier couples were generated using the population register of the SLSJ region kept at SOREP. The mean coefficient of inbreeding was only slightly elevated in the tyrosinemic group compared with the control groups and was due to remote consanguinity. The mean kinship coefficient was 2.3 times higher in the tyrosinemic group than in the control groups. In the SLSJ region the places of origin of the tyrosinemic children and their parents did not show a clustered nonuniform distribution. Endogamy was not found to be higher in the tyrosinemic group than in the control groups. All these results support both the hypothesis of a founder effect for tyrosinemia and a high gene frequency in northeastern Quebec.     

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.     

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.     

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     

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.     

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.     

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.     

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.     

Neurofibromatose Typ 2

Neurofibromatosis type 2 (NF2) is a genetic autosomal-dominant disorder characterized by multiple benign tumors of the nervous system. Bilateral vestibular schwannomas, known as acoustic neuromas, are the hallmark of NF2 and can be found in more than 90% of patients, causing progressive hearing loss and not infrequently leading to deafness. Spinal tumors (schwannoma, meningioma and ependymoma) develop with similarly high frequency among NF2 patients, while approximately only 1/3 of these lead to neurological symptoms. Cranial non-vestibular schwannomas and meningiomas are also frequent in NF2 patients. The clinical spectrum of NF2 further includes ophthalmological lesions and polyneuropathy. With a birth incidence of around 1 in 25,000, the genetic cause for NF2 is the heterozygous inactivation of the NF2 tumor suppressor gene on 22q. More than half (50%–80%) of NF2 patients are found to bear de novo mutations which are frequently present in a mosaic fashion (25%–30%). This review presents clinical and genetic aspects of NF2, as well as recent developments in its pharmacological treatment.     

Gene for hereditary neuropathy with liability to pressure palsies (HNPP) maps to chromosome 17 at or close to the locus for HMSN type 1

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder with an increased susceptibility of peripheral nerves to mechanical lesions resulting in transient nerve palsies. Many carriers remain asymptomatic but can be traced by electrophysiological examination, thereby demonstrating that HNPP is a generalised polyneuropathy. By using highly polymorphic markers linkage analysis was performed in a large family with HNPP. This resulted in a maximum lod score of 4.20 at =0.10 with D17S520. Three-point linkage suggests that the gene for HNPP is located on chromosome 17 in the region between D17S250 (q11.2–q12) and D17S520 (p12), a region that has recently been shown to encompass a locus for another hereditary neuropathy, hereditary motor and sensory neuropathy type 1 (HMSN type 1). This raises the possibility that HNPP and this form of HMSN type 1 are allelic. In keeping with this speculation is our recent finding that D17S122, another marker from the HMSN type 1 region, displays apparent loss of heterozygosity in this family.     

Treatment of symptomatic diabetic neuropathy by surgical decompression of multiple peripheral nerves.

Symptomatic diabetic sensorimotor polyneuropathy is considered progressive and irreversible. The hypothesis that symptoms of diabetic neuropathy may be due to entrapment of peripheral nerves was investigated in a prospective study from 1982 to 1988 in which diabetics (38 type I, 22 type II) had surgical decompression of 154 peripheral nerves in 51 upper extremities and 31 lower extremities. Mean postoperative follow-up was 30 months (range 6 to 83 months). Considering the entire series, an excellent final result was noted for motor function in 44 percent and for sensory function in 67 percent of the decompressed nerves. Ten percent of the patients were not improved, and 2 percent were worse in sensorimotor function. Upper extremity nerve decompressions achieved better results than lower extremity nerve decompressions. Improvement in postoperative electrodiagnostic studies varied in relationship to the preoperative electrodiagnosis. Improvement was noted in 100 percent of those nerves with the preoperative diagnosis of "localized entrapment," 80 percent for "peripheral neuropathy with superimposed entrapment," and 50 percent for "peripheral neuropathy." Progressive neuropathy occurred in a nontreated limb of 50 percent of those patients whose surgically treated limb maintained improvement. The results of this study suggest that symptoms of sensorimotor diabetic neuropathy may be due partly to compression of multiple peripheral nerves. The results further suggest that surgical decompression of such nerves may result in symptomatic improvement.     

Crypt cell development in newborn rat small intestine

Three monoclonal antibodies were prepared against luminal membranes from small intestinal cells of 3-d-old rats (YBB 1/27, YBB 3/10) and crypt cell membranes from adult rats (CC 4/80). The antibodies were shown to define specific stages of development of the intestinal crypt cells. The YBB 1/27 antigen was first detected at the luminal membrane of the epithelial cells in fetal intestine at day 20 of gestation; it was confined to the crypt cells and lower villus cells between 1 and 20-22 d after birth, and could not be detected in any region of the intestine in older animals. The YBB 3/10 antigen, identified as a set of high Mr proteins, was localized over the entire surface membrane of fetal intestinal cells and of crypt and villus cells after birth; after weaning (20-22 d after birth) it gradually disappeared from the villus cells and became confined to the region of the crypts. The CC 4/80 antigen, identified as a protein (or a set of related proteins) of molecular mass 28-34 kD, was shown to appear in the crypt cells 10-14 d after birth. Its distribution changed after weaning, when it disappeared from the crypts, and was localized in the absorptive lower villus cells. This change in pattern could, in part, be prematurely elicited by cortisone injection in younger animals. These results have demonstrated the presence of specific surface membrane components on the intestinal crypt cells, and suggested that fetal antigens may be retained in these cells after birth.     

Azithromycin in the extremely low birth weight infant for the prevention of Bronchopulmonary Dysplasia: a pilot study

Background

Azithromycin reduces the severity of illness in patients with inflammatory lung disease such as cystic fibrosis and diffuse panbronchiolitis. Bronchopulmonary dysplasia (BPD) is a pulmonary disorder which causes significant morbidity and mortality in premature infants. BPD is pathologically characterized by inflammation, fibrosis and impaired alveolar development. The purpose of this study was to obtain pilot data on the effectiveness and safety of prophylactic azithromycin in reducing the incidence and severity of BPD in an extremely low birth weight (≤ 1000 grams) population.

Methods

Infants ≤ 1000 g birth weight admitted to the University of Kentucky Neonatal Intensive Care Unit (level III, regional referral center) from 9/1/02-6/30/03 were eligible for this pilot study. The pilot study was double-blinded, randomized, and placebo-controlled. Infants were randomized to treatment or placebo within 12 hours of beginning mechanical ventilation (IMV) and within 72 hours of birth. The treatment group received azithromycin 10 mg/kg/day for 7 days followed by 5 mg/kg/day for the duration of the study. Azithromycin or placebo was continued until the infant no longer required IMV or supplemental oxygen, to a maximum of 6 weeks. Primary endpoints were incidence of BPD as defined by oxygen requirement at 36 weeks gestation, post-natal steroid use, days of IMV, and mortality. Data was analyzed by intention to treat using Chi-square and ANOVA.

Results

A total of 43 extremely premature infants were enrolled in this pilot study. Mean gestational age and birth weight were similar between groups. Mortality, incidence of BPD, days of IMV, and other morbidities were not significantly different between groups. Post-natal steroid use was significantly less in the treatment group [31% (6/19)] vs. placebo group [62% (10/16)] (p = 0.05). Duration of mechanical ventilation was significantly less in treatment survivors, with a median of 13 days (1–47 days) vs. 35 days (1–112 days)(p = 0.02).

Conclusion

Our study suggests that azithromycin prophylaxis in extremely low birth weight infants may effectively reduce post-natal steroid use for infants. Further studies are needed to assess the effects of azithromycin on the incidence of BPD and possible less common side effects, before any recommendations regarding routine clinical use can be made.     

Peer-rearing influences subsequent maternal behavior and infant survival in a newly formed herpes B-virus negative rhesus macaque group

The maternal behavior of primiparous rhesus macaques (Macaca mulatta), peer-reared since 1/2 years(s) of age as part of aHerpesvirus simiae (herpes B-virus) screening protocol, was examined and compared to a control group of conspecifics reared in their natal group. Infant survival was significantly higher in control groups as compared to the test group, a result attributed to the high incidence of infant kidnapping/abandonment in the test group. Among the test subjects, infant survival rate increased as the birth season progressed, thus it is possible that exposure to mothers/infants helped in the maternal success of those females who gave birth later in the season. Test group infants were touched by group members significantly more than the infants of control subjects, whereas these infants were groomed by their mothers and in a ventral position for a greater time relative to the infants of the test subjects. This study suggests that females, partially reared in peer groups, may be at early risk for maternal incompetence and consequent greater infant mortality, and that exposure to mother-infant dyads may augment the proficiency of maternal skills.     

Spatial and temporal distribution of cystic fibrosis and of its mutations in Brittany,France: a retrospective study from 1960

Cystic fibrosis (CF) is the most common severe inherited disorder that affects children in Caucasian populations. The aim of this study was to define the spatial and temporal distribution of CF and its mutations in Brittany (western France) where the frequency of the disease is high. We retrospectively registered all CF patients born in Brittany since 1960 by cross-checking various data sources (e.g. medical care centres, genetics laboratories, hospital archives). Councils were contacted so that the place of residence of patients at birth could be determined. Moreover, the spectrum of CF transmembrane conductance regulator (CFTR) mutations and their spatial distribution across Brittany were determined. A total of 520 patients was registered in this study. The incidence of CF was assessed according to administrative (department, district) and diocesan divisions of Brittany and its evolution analysed over four decades. The incidence of CF was 1/2630, with a west/east gradient that was confirmed over time (Finistère: 1/2071 vs Ille-et-Vilaine: 1/3286). At present, the incidence of CF is decreasing, mainly as a result of prenatal diagnosis. An excellent mutation detection rate of 99.7% was obtained. Western Brittany presented a specific spectrum of mutations: 1078delT (9.4% of mutated alleles in the diocese of Cornouaille), G551D (7.7% in the diocese of Léon), 4005+1G-->A (2.9% in Cornouaille) and W846X (1.5% in western Brittany). On the other hand, the eastern region showed a spectrum more similar to the overall picture in France as a whole. This study enabled a precise measurement of the incidence of CF in Brittany to be obtained. The high frequency of the CFTR mutated alleles may result from founder effects and genetic drifts. Moreover, the study brings together the regional specificities of the CFTR gene and highlights disparities that exist in this part of France, both in incidence and in mutation distribution. These are attributable to different degrees of isolation and of population movements between the eastern and western parts of the region. Given that this is the first time that such a detailed study of the CFTR gene has been performed on a large population, this heightened knowledge of the epidemiology of CF in Brittany should provide a basis for the improvement of diagnostic strategies and refinement of genetic counselling.     

Prenatal diagnosis of trisomy 21: registration results from a single genetic center

This is a retrospective review of all collected amniotic fluid samples, chorionic villus samples and other fluid-aspirations (hygroma colli fluid/urine from megacystis) over an 11-year period (1996-2006) in a single Genetic Center (University Hospital Gasthuisberg, Leuven), looking at the prenatal diagnosis of trisomy 21. In this study a total of 404 diagnoses of trisomy 21 were made on 29696 samples (1.4%). The prenatal diagnosis of trisomy 21 increased over the years with 0.88% (21/2363) in 1996 and 1.99% (50/2512)in 2006. Also the type of invasive testing changed over the years with an increase of the proportion of trisomy 21- diagnoses by chorionic villussampling from 2001. Looking at the registry for perinatal activities in Flanders for the year 2006 the live birth incidence for trisomy 21 was 1/1782 and this is lower than the often reported incidence oftrisomy 21 at birth of 1/800: it is likely that the use of more sensitive screening methods for the prenatal detection of trisomy 21 and the election of termination for most affected pregnancies affects the birth incidence oftrisomy 21.     

Genes to diseases (G2D) computational method to identify asthma candidate genes

Asthma is a complex trait for which different strategies have been used to identify its environmental and genetic predisposing factors. Here, we describe a novel methodological approach to select candidate genes for asthma genetic association studies. In this regard, the Genes to Diseases (G2D) computational tool has been used in combination with a genome-wide scan performed in a sub-sample of the Saguenay-Lac-St-Jean (SLSJ) asthmatic familial collection (n = 609) to identify candidate genes located in two suggestive loci shown to be linked with asthma (6q26) and atopy (10q26.3), and presenting differential parent-of-origin effects. This approach combined gene selection based on the G2D data mining analysis of the bibliographic and protein public databases, or according to the genes already known to be associated with the same or a similar phenotype. Ten genes (LPA, NOX3, SNX9, VIL2, VIP, ADAM8, DOCK1, FANK1, GPR123 and PTPRE) were selected for a subsequent association study performed in a large SLSJ sample (n = 1167) of individuals tested for asthma and atopy related phenotypes. Single nucleotide polymorphisms (n = 91) within the candidate genes were genotyped and analysed using a family-based association test. The results suggest a protective association to allergic asthma for PTPRE rs7081735 in the SLSJ sample (p = 0.000463; corrected p = 0.0478). This association has not been replicated in the Childhood Asthma Management Program (CAMP) cohort. Sequencing of the regions around rs7081735 revealed additional polymorphisms, but additional genotyping did not yield new associations. These results demonstrate that the G2D tool can be useful in the selection of candidate genes located in chromosomal regions linked to a complex trait.     

Impact of public health strategies on the birth prevalence of cystic fibrosis in Brittany,France

Taking into account the situation of Brittany, a region of western France where cystic fibrosis (CF) is common and where a neonatal screening program was set up 14 years ago, the aim of this study was to determine the way in which the birth prevalence of CF has been influenced by the various public health strategies implemented in the region (neonatal screening, prenatal diagnosis, ultrasound examination and family testing). This study used the results of the neonatal screening program, which enabled a precise measure of the prevalence of CF at birth to be obtained. Over the same period, we collected data from prenatal diagnoses carried out in the region, first in families related to a CF child and also those made following the detection of an echogenic bowel upon routine ultrasound examination performed during pregnancy. The prevalence of CF at birth was estimated to be 1/2838 in the region over a 10-year period (1992-2001). By including the 54 CF-affected pregnancies that were terminated during these 10 years, the corrected birth prevalence of CF was 1/1972. Prenatal diagnosis was therefore responsible for a global decrease in CF prevalence at birth of 30.5%. This work constitutes the first study able to provide a precise measure of CF birth prevalence and of its evolution through the combined effects of neonatal screening, prenatal diagnosis, ultrasound examination and family testing.     

Calf survival from embryo transfer-induced twinning in dairy-beef cows and the effects of synchronised calving

In each of 4 years, 94-116 mature cows had two 6-7-day-old embryos, produced by the in vitro fertilisation of oocytes, inserted non-surgically into one uterine horn of each cow. Starting 5 days before the expected date of calving, the cows were continuously observed and assistance at calving was provided when required. In year 1, perinatal calf survival was similar in twin-calving (TC) and single-calving (SC) cows (98.1 versus 100% for calves born to TC and SC, respectively). There was a higher incidence of assistance at birth for TC (52%) than for SC (21%). In years 2 and 3, the calving of 30 SC and 33 TC was synchronised using an injection of Opticortinol (OP) 6-9 days before the injection of Estrumate and Dexol-5 (E+D). A further 34 SC calved naturally. Synchronised calving reduced the spread of calving from 16-25 to 8-9 days without reducing perinatal calf survival and had no significant effect on the incidence of assistance at birth in SC. The TC in years 2 and 3 had a high incidence of retained placenta at 48 h (70%) and a high incidence of assistance at birth (85%). In year 4, calving was synchronised in 16 SC and 21 TC with E+D and no pre-treatment with OP, while 15 SC were treated with both OP and E+D. There were no effects of the hormone treatment on perinatal calf survival and only small effects on the incidence of assisted births for SC. The incidence of retained placenta at 48 h was lower for SC pre-treated with OP (40%) than for SC (88%) and TC (76%) not pre-treated with OP. Continuous supervision over calving produced perinatal calf survival rates for TC that were similar to SC, despite the higher incidence of assistance of TC at parturition. Hormonal synchronisation of calving can halve the time required for continuous supervision of calving, but the hormone treatments exacerbate the already high incidence of retained placenta in TC.     

Association of polymorphic markers of lipid metabolism genes with diabetic polyneuropathy in type 1 diabetes mellitus

The aim of this study was the search of association with diabetic polyneuropathy of the polymorphic markers epsilon2/epsilon3/epsilon4 of apolipoprotein E (APOE) and I/D of apolipoprotein B (APOB) genes in groups of type 1 diabetes patients with diabetic polyneuropathy (n = 86) and without its clinical signs (n = 94). We have not found significant association with diabetic polyneuropathy (DPN) of epsilon2/epsilon3/epsilon4 marker of APOE gene. However the comparison of allele and genotype frequencies of I/D marker of APOB gene showed that the carriers of I allele and II genotype had higher risk (OR = 1.66 and 2.01, relatively; p < 0.027), whereas the carriers of D allele had lower risk of DPN (OR = 0.60; p < 0.018). Our findings show that APOB gene, encoding one of the main components of lipid metabolism system, is involved into the diabetic polyneuropathy development in type 1 diabetes mellitus.