Skew in the human caveolin 1 gene upstream purine complex homozygote haplotype compartment in multiple sclerosis.

Caveolin 1 (CAV1) is a component of the myelin sheath and the expression of the gene encoding this protein is increased during myelination in Schwann cells and oligodendrocytes. We sought to investigate the homozygote haplotype compartment in a recently identified polymorphic purine complex at the upstream region of the human CAV1 gene in multiple sclerosis (MS). In a case/control study design, the region was characterized in 126 cases of MS diagnosed based on the Revised McDonald diagnostic criteria, and 460 controls. We report a skew in the homozygote haplotype compartment in the cases versus controls both in a qualitative and quantitative respect. Excess homozygosity for haplotypes was observed in the MS cases (corrected p<0.012, OR=2.54, CI 1.14-5.64). Furthermore, we observed eight homozygote haplotypes in the MS cases that were non-existent in the controls (p<0.0003, OR=20.27, CI 2.50-163.8). For the first time, our data highlight the CAV1 upstream purine complex as a novel susceptibility genomic locus in the pathophysiology of MS. Of utmost importance, the region has been conserved across species, including mouse, guinea pig, rhesus macaque, and human. The functional effect of this region remains to be clarified in the future studies.

Population screening for association of mitochondrial haplogroups BM, J, K and M with multiple sclerosis: interrelation between haplogroup J and MS in Persian patients.

BACKGROUND: Multiple sclerosis (MS) is an immunological inflammatory disease of the central nervous system (CNS) which is chronically observed in young adults. On the basis of earlier studies, potential relatedness between MS and mitochondrial DNA (mtDNA) mutations was postulated. MATERIALS AND METHODS: 246 individuals were screened using the PCR-RFLP method, including 70 MS patients examined for mitochondrial haplogroups BM, J, K and M and 176, 149 and 70 normal controls examined for haplogroups BM and M, J and K, respectively. RESULTS AND DISCUSSION: Our analysis revealed a relatively high proportion of haplogroup BM in MS patients (approximately 26%) compared to normal controls ( approximately 13%). In addition, a slightly significant increase of MS patients of haplogroup J (20% in MS patients versus 9.39% in normal controls at P =0.049), while haplogroups M and K did not show contribution to MS contingency (2.85 and 2.27%, respectively at P = 1.000 in haplogroup M and 12.85 and 7.14% respectively at P =0.399 in haplogroup K).

Mitochondrial DNA and Y-chromosome variation in the caucasus.

We have analyzed mtDNA HVI sequences and Y chromosome haplogroups based on 11 binary markers in 371 individuals, from 11 populations in the Caucasus and the neighbouring countries of Turkey and Iran. Y chromosome haplogroup diversity in the Caucasus was almost as high as in Central Asia and the Near East, and significantly higher than in Europe. More than 27% of the variance in Y-haplogroups can be attributed to differences between populations, whereas mtDNA showed much lower heterogeneity between populations (less then 5%), suggesting a strong influence of patrilocal social structure. Several groups from the highland region of the Caucasus exhibited low diversity and high differentiation for either or both genetic systems, reflecting enhanced genetic drift in these small, isolated populations. Overall, the Caucasus groups showed greater similarity with West Asian than with European groups for both genetic systems, although this similarity was much more pronounced for the Y chromosome than for mtDNA, suggesting that male-mediated migrations from West Asia have influenced the genetic structure of Caucasus populations.

Consanguineous marriage in Iran.

Consanguineous marriage is a major feature of family systems in south-west Asia. The aim of the present study was to determine the current prevalence and patterns of consanguinity in Iran as a means of assessing the associated requirement for genetic counselling services. Consanguinity was studied in 12 ethnic/religious populations, the Persians (Shi'a and Sunni), Kurds (Shi'a and Sunni), Lurs, Azaris, Baluchis, Zabolis, Turkamans, Bakhtiaris, Ghashghais and Arabs. A multi-stage sampling design was used with a representative total sample of 306 343 couples. The overall rate of consanguineous marriage was 38.6% with a mean inbreeding coefficient (alpha) of 0.0185. First cousin marriages (27.9%) were the most common form of consanguineous union, with parallel patrilateral marriage especially favoured. Statistically significant differences were observed in the prevalence and patterns of consanguinity between ethnic/religious populations and geographical regions. There also were significant differences for proportions of consanguineous marriages between Shi'a and Sunni populations within the same ethnic group. The highest rates of consanguineous union were in the least affluent sections of the population.

Dermatoglyphics in patients with eczema, psoriasis and alopecia areata.

BACKGROUND/AIMS: The study of patterns of fingerprints is important in anthropology and medical genetics, chiefly because of their diagnostic usefulness. In the present work, we studied the frequencies of various types of skin ridges of the first phalanx in patients with eczema, psoriasis and alopecia areata. METHODS: In a double-blind case-control study, we determined the frequencies of fingerprints in 551 patients (240 cases with eczema, 164 cases with psoriasis and 147 cases with alopecia areata) as well as in general population of Hamadan City (control group: 188 males and 529 females). We compared the frequencies between various fingers, hands and sexes in all three case groups as well as between case groups and control group. RESULTS: The frequencies of various types of fingerprints are presented in some tables. The results showed that frequencies are not statistically different according to types of fingers, hands (left or right) and sexes as well. But they are significantly different in various case groups and between case groups and control group. CONCLUSIONS: We can conclude that frequencies of various patterns of skin ridges differ in eczema, psoriasis and alopecia areata from normal population.

Serum protein polymorphisms (HP, TF, GC and PI) in four Iranian population samples.

A total of 960 individuals from four Iranian population samples (Tabriz, Tehran, Yazd, Mashhad) was typed for HP and for TF, GC and PI subtype polymorphism. Statistically significant intergroup heterogeneity in the distribution of allele frequencies was found only in the HP polymorphism. Comparisons with other Iranian populations suggest considerable ethnic differences with regard to the TF and GC subtype polymorphisms. Some rare alleles were observed in all four samples (Tabriz: GC*1C1; Tehran: PI*S: Yazd: PI*S; Mashhad: PI*Z).

The ITI system in South Koreans and Iranians analysed by an improved classification procedure. Distribution of alleles and description of "new" phenotypes.

Phenotype and gene frequency distributions of the inter-alpha-trypsin inhibitor (ITI) system were analysed in populations from southern Korea and from Iran. The gene frequencies of the common alleles ITI*I and ITI*2 were 0.532 and 0.422, respectively, in southern Korea, and 0.612 and 0.354, respectively, in Iran. The postulated third allele, ITI*3, was found in the homozygous form. Gene frequencies of this rare allele were calculated to be 0.042 and 0.029 in Korea and Iran, respectively. Two additional rare alleles, ITI*4 and ITI*5, determine further phenotypes found in the population from Taejon (Korea) and Iran, respectively, in combination with the common ITI*2 allele. Gene frequencies of ITI*4 and ITI*5 were calculated to be 0.006 and 0.005, respectively. For phenotype classification, untreated sera were separated by isoelectric focusing (IEF) on polyacrylamide gels followed by immunoblotting.

Investigations on the ethnic variability of the ABO blood group polymorphism in Iran.

112 Iranian population samples with a total of 600954 individuals are analyzed concerning the ethnic variability of ABO allele frequencies. The genetic heterogeneity within and between these population samples is considerable. This heterogeneity is discussed with regard to the ethnohistory of Iran. The most striking ABO allele frequencies are observed in Assyrians, Armenians and Zoroastrians, which differ extremely from that of all the other hitherto studied ethnic groups of Iran. Obviously varying ABO allele frequencies are seen also in Yazdis as well as in Turkomans and Arabs living in Iran. And finally the Iranian Jews reveal clear frequency differences in comparison with all the other Iranian population groups. It can be assumed that the specific ABO allele frequencies found in the above mentioned ethnic groups are connected with their different geographical origin as well as with their marked endogamy.

Alpha-1-antitrypsin types and serum levels in toxoplasmosis.

alpha 1-Antitrypsin (PI) types were studied in patients with toxoplasmosis (n = 84) and controls (n = 143) using isoelectric focusing. The patients showed a lower frequency of rare types (p less than 0.025) and a higher frequency of individuals with increased PI levels (p less than 0.005) compared to controls.

Transferrin subtypes in Iran.

The frequency of transferrin Tf C subtypes has been determined by double one-dimensional electrophoresis of plasma samples from Moslems (n = 91), Zoroastrians (n = 97), Jews (n = 88) and Armenians (n = 88) of Iran. The Zoroastrians show the lowest frequency of TfC1 (0.4999) and highest frequencies of TfC2 and TfC3 (.02215, and 0.2783, respectively). The Jews have the highest TfC1- and the lowest TfC2- and TfC3 frequencies (0.8011, 0.1478, and 0.0512, respectively). It could be shown that the differences between Zoroastrians and Jews are highly significant (p less than 0.001). Arbitrary subtyping of transferrin Tf B and TfD phenotypes could be done on samples from three regional groups of Iran: North: n = 282, Central: n = 548, and South: n = 587 into Tf B (Iran 1, 2, 3 and 4) and Tf D (Iran 1, 2 and 3) was performed according to mobilities relative to the transferrin C protein during polyacrylamide gel electrophoresis and by relative pI deviations from the Fe2-transferrin C1 protein after isoelectric focussing. The allele frequencies found in the total sample (n = 1417) are: TfB1 = 0.0003, TfB2 = 0.0010, TfB3 = 0.0042, TfB4 = 0.0007; TfD1 = 0.0017, TfD2 = 0.0014, and TfD3 = 0.0010.

Oto-palato-digital syndrome in an Iranian infant.

A male infant is presented with wide fontanels, micrognathia, mid-face hypoplasia, hypertelorism, broad nasal root, down-slanting palpebral fissures, small thorax, funnel chest, short wide toes, camptodactyly and cutaneous syndactyly of fingers and toes, dysplastic bones with thin wavy ribs and bowed femore, cryptorchidism, and hypospadias grade I. The mother of this infant showed some signs of the same condition, including hypertelorism, micrognathia, small nose with depressed bridge, flat mid-face, impacted teeth and small chest. This case shows many similarities to oto-palatal-digital syndrome types I and II.

Serum proteins and erythrocyte enzymes of populations in Iran.

The genetic polymorphisms of nine biochemical genetic markers were investigated in four populations (Turks, Kurds, Tehranis and Kermanis) living in the north-east and south-east regions of Iran. Only one of the nine loci studied (acid phosphatase) showed significant gene frequency differences and for the C3 system the F allele frequencies in these populations were the lowest ever reported from Iran.

Congenital hereditary lymphedema (Nonne/Milroy).

A 36-year-old man, with his children, a three-year-old girl, and a five month-old boy, suffering from congenital hereditary lymphedema, were the subjects of the present study. The man and his wife, were distant relatives. All the other family members of the two sides were apparently healthy.

A new transferrin variant from Iran (Tf B-Iran): review of 36 variant alleles.

A total of 2581 serum samples collected from five population groups of Iran was studied for electrophoretic variations of the transferrin (Tf). Besides the common phenotype Tf C the authors could observe 41 individuals with rare Tf types: CB1, CB2, CD1, CDChi, CD2. In addition to these Tf types two individuals with a new Tf B variant were observed. This new variant was found in the Dezfooli sample and was designated as Tf B-Iran. The electrophoretic position of this variant is described, and all the hitherto known Tf variants are reviewed.

Thyroidal radioactive iodine uptake in Iran.

The thyroidal uptake of iodine in 356 goitrous patients in Tehran and Mashad (two major cities in Iran) was studied. 131I was orally administered at the doses 10 to 50 microCi and the uptake was measured 2 and 24 hours following administration. The results demonstrate that the iodine deficiency is the main cause of goitre in these two cities and that the deficiency in Mashad is more severe than in Tehran.

Congenital malformations and genetic diseases in Iranian infants.

Data of 13,037 live-born infants from a hospital in Tehran, Iran were analysed for congenital malformations and genetic diseases. The results showed that the rates of joint dislocation, cleft lip, cleft palate and finger anomalies are similar to those of the other populations. The rates of chromosomal, thorax and abdominal, external genital anomalies and other syndromes were higher compared with other populations, whereas the rates of multiple births and limb anomalies were lower.

Annuality of birth, delivery types and sex ratio in Tehran, Iran.

616,638 births during 1967-1983 from a maternity hospital in Tehran (Iran) have been considered for the present study. The mean rate of normal delivery was 92.59%, that of Caesarean was 3.09%, that of wantose was 1.52% and finally that of forceps was 1.31%. Caesarean and wantose (vacuum extractor) delivery types showed an increasing trend, whereas the normal and forceps delivery types showed a decreased trend during the period under study. The secondary sex ratio was the highest in 1977 and the lowest in 1983 with a mean of 105.18. The twinning rate showed a decreasing trend during the above period.

PIP: 616,638 births during the 1967-83 period in a maternity hospital in Tehran, Iran, were studied in an effort to report various types of delivery and sex ratio as well as the rate of multibirths over this 17-year period. Table 1 shows the annual births for males and females during 1967-83. It is evident that the highest birth numbers occurred in 1974--41,196--and the lowest in 1978--29,344. Table 2 shows the types of delivery. Normal delivery ranged from 95.68% in 1969 to 88.18% in 1978 with a mean of 92.59%. Cesarean delivery increased from 1.80% in 1967 to 6.36 in 1983. Forceps delivery type showed different frequencies--from 0.23% (1970-71) to 2.80% (1967). Wantose delivery type also showed different frequencies from nil (1976) to 3.84% (1979). Figure 1 shows the changes of the secondary sex ratio. The secondary sex ratio ranged from 102.67 in 1982 to 107.26 in 1977 with a mean of 105.18. Table 3 shows the rate of multibirths. The rate of twins has had different frequencies--from 1/75.13 births (1967) to 1/115.45 births (1982 with a total mean of 1/94.42 births. Twin births decreased over the period. The triplet births also showed different rates--1/4552.89 births (1968) to 1/302,207 births (1978) with a total mean of 1/14,014.5 births. Quadruplets occurred only once (1979). The study shows that the birth number depends on the economic and political factors--a high number in 1971 which was nearly the beginning of the economic development in Iran and by the lowest number in 1978 which was the prerevolutionary period. Sex ratio increased during 1976-78 because of the migration of the rural population to Tehran. Consequently, the changes of the secondary ratio over the 17-year period have been influenced by the said factors of the time of insemination and the couples' sexual activity. These factors are influenced by the economic, geographic, and psychic environment, nutrition, and other cultural factors. Many social factors for sex ratio and the rate of the secondary sex ratio are responsible for influencing the trend of delivery types, especially for the decreased trend of normal delivery and the increased trend of Cesarean delivery types.