ABSTRACT
Mutations in the IDUA gene cause deficiency of the lysosomal enzyme alpha-l-iduronidase (IDUA), which leads to a rare disease known as mucopolysaccharidosis type I. More than 300 pathogenic variants of the IDUA gene have been reported to date, but not much is known about the distribution of mutations in different populations and ethnic groups due to the low prevalence of the disease. This article presents the results of a molecular genetic study of 206 patients with mucopolysaccharidosis type I (MPS I) from the Russian Federation (RF) and other republics of the former Soviet Union. Among them, there were 173 Russian (Slavic) patients, 9 Tatars, and 24 patients of different nationalities from other republics of the former Soviet Union. Seventy-three different pathogenic variants in the IDUA gene were identified. The common variant NM_000203.5:c.208C>T was the most prevalent mutant allele among Russian and Tatar patients. The common variant NM_000203.5:c.1205G>A accounted for only 5.8% mutant alleles in Russian patients. Both mutations were very rare or absent in patients from other populations. The pathogenic variant NM_000203.5:c.187C>T was the major allele in patients of Turkic origin (Altaian, Uzbeks, and Kyrgyz). Specific own pathogenic alleles in the IDUA gene were identified in each of these ethnic groups. The identified features are important for understanding the molecular origin of the disease, predicting the risk of its development and creating optimal diagnostic and treatment tools for specific regions and ethnic groups.
ABSTRACT
AIM: To study the influence of 444 G/A (rs 1108580) and -1021 C/T (rs 1611115) polymorphisms of the dopamine beta-hydroxylase (DBH) gene on clinical parameters of the trajectory of alcohol dependence. MATERIAL AND METHODS: Authors studied 548 male inpatients, of Slavic ethnicity, with ICD-10 diagnosis of «alcohol dependence¼ (F-10.2). RESULTS: The effects of DBH * 444 G/A on the rate of formation of alcohol withdrawal syndrome (AWS), and DBH *-1021C/T on the age of onset of alcohol abuse with significant role of the age of first alcohol use were identified. In 444 G/A GG carriers, the development of AWS was accelerated since the beginning of alcohol abuse compared with AA carriers (p=0.026), AG carriers occupied an intermediate position. In 22.5% of GG carriers, AWS developed within 2 years (AA: 8.11%, p=0.005; AG: 17.67%, p=0.04). According to the results of linear regression analysis, in AG carriers the alcohol abuse (p=0.037) and the AWS (p=0.049) developed earlier than in AA carriers if the first alcohol use occured at the age of about 15 years. Among -1021C/T genotype carriers who began to abuse alcohol at an early age (before 20 years), there were 23.45% patients with CC genotype and only 11.97% with a T allele (genotypes CT+TT) (p=0.03), but T carriers began to abuse alcohol earlier than others (p=0.05) if the first alcohol use occurred at the age of about 16 years. CONCLUSION: The results can be used to search for genetic markers for prognosis of alcohol dependence development.
Subject(s)
Alcoholism/genetics , Alcoholism/psychology , Dopamine beta-Hydroxylase/genetics , Adult , Alleles , Ethanol/adverse effects , Genetic Markers , Humans , International Classification of Diseases , Male , Middle Aged , Polymorphism, Genetic , Substance Withdrawal Syndrome/geneticsABSTRACT
AIM: A quantitative assessment of the impact of genetic factors (density of family history of alcohol dependence and dopamine system genes polymorphisms) on the average time to relapse (ATR) after alcohol dependence treatment (duration of therapeutic remission from alcohol dependence). MATERIAL AND METHODS: Authors studied 247 male Russian inpatients diagnosed with ICD-10 F10.2 who had at least two therapeutic remissions before the current hospitalization and 259 healthy controls. ATR and the density of family history of alcohol dependence were evaluated retrospectively according to the clinical interview. RESULTS AND CONCLUSION: The high density of family history (at least 2 people with alcohol problems among the blood relatives) and some dopamine system genes polymorphisms significantly affect the average time to relapse. An allele A9 of the dopamine transporter gene (DAT VNTR 40 bp) was associated (p=0.003; OR=1.73) with short (up to 12 months) average time to relapse. A trend toward association (p=0.052) was noted for dopamine receptor type 2 gene polymorphisms (rs1800497, rs6275). Patients with long-term ATR are genetically different from patients with short ATR by the set of variants of tyrosine hydroxylase gene (HUMTH01, p=0.002; OR=3.08) and from the control group by the genotype LH of the catechol-O-methyltransferase gene (rs4680, p=0.02; OR=2.33). Some other sets of HUMTH01 variants (p=0.0001; OR=2.38) and the dopamine receptor type 4 (DRD4 VNTR 48 bp, p=0.055) may have protective properties with regard to short ATR. Polymorphisms (rs1108580, rs1611115) of the dopamine-beta-hydroxylase gene were not related to the ATR.
ABSTRACT
Sixty blood samples from pregnant women during gestational weeks 9-28 were investigated. Cell-free fetal DNA was extracted from maternal plasma or serum to be detected by nested PCR for determination of fetal gender. The SRY gene as a marker for fetal Y chromosome was detected in 34/36 women carrying a male fetus. In 3/24 women carrying female fetuses, the SRY sequence was also detected. Overall, fetal sex was correctly predicted in 91.7% of the cases. Therefore, the new, non-invasive method of prenatal diagnosis of fetal gender for women at risk of producing children with X-linked disorders is reliable, secure, and can substantially reduce invasive prenatal tests.
