Natural killer cell immunoglobulin-like receptor (KIR) locus profiles in African and South Asian populations

Natural killer (NK) and some T cells express killer cell immunoglobulin-like receptors (KIRs), which interact with HLA class I expressed by target cells and consequently regulate cytolytic activity. The number of KIR loci can vary and so a range of genetic profiles is observed. We have determined the KIR genetic profiles from one African (n = 62) and two South Asian (n = 108, n = 78) populations. Several of the KIRs are present at significantly different frequencies between the two major ethnic groups (eg KIR2DS4 gene frequency 0.82 African, 0.47 S Asian. Pc < 1 x 10(-6)) and this is due to uneven distribution of two KIR haplotype families 'A' and 'B'. All three populations described here displayed a greater degree of diversity of KIR genetic profiles than other populations investigated, which indicates further complexity of underlying haplotypes; in this respect we describe two individuals who appear homozygous for a large deletion including the previously ubiquitous 2DL4. We have also reanalysed three populations that we studied previously, for the presence of a KIR which is now known to be an indicator of the 'B' haplotype. South Asians had the highest overall frequencies of all KIR loci characteristic of 'B' haplotypes (Pc < 0.0001 to < 0.004). Furthermore, gene frequency independent deviances in the linkage disequilibrium were apparent between populations.

Lipoprotein-genotype associations in Trinidadian neonates

OBJECTIVES: We hypothesized that common variation in the angiotensinogen (AGT), beta-3-adrenergic receptor. intestinal fatty acid-binding protein, serum paraoxonase, paraoxonase-2, hepatic lipase, apolipoprotein E (APOE), and Werner helicase (WRN) genes would be associated with variation in biochemical phenotypes in a previously unstudied neonatal sample. DESIGN AND METHODS: We examined associations of both nongenetic and genetic variables with plasma lipoprotein traits in neonates from Trinidad. RESULTS: Among nongenetic variables, we found significant associations between plasma concentrations of 1.) lipoprotein (a) [Lp(a)] and both ethnicity (p=0.037) and birth weight (p=0.001); 2)total cholesterol and gender (p=0.010); 3)triglyceride and birth weight (p=0.035); and 4)apolipoprotein A1 and gender (p=0.016). Among genetic variables, we found that: 1)common variation on chromosome 1q in AGT codon 235 was significantly associated with variation in plasma apolipoproteins Al (p<0.0001); and 3)common variation in APOE at codons 112 and 158 was significantly associated with variation in plasma triglycerides (p=0.013). CONCLUSIONS: The associations with AGT and WRN are novel and may have resulted either from direct influence of the genetic variants or through linkage disequilibrium with other functional loci, such as the familial combined hyperlipidemia locus on chromosome 1q in the case of AGT. Despite the fact that there are some limitations in making determinations from cord blood, the results suggest that there may be genetic determinants of plasma lipoproteins in neonates. (AU)

Association of PON2 variation with birth weight in Trinidadian neonates of South Asian ancestry

Variation in the PON1 and PON2 genes has been shown to be associated with coronary heart disease risk in adults of South Asian origin. In this group, low birth weight is also associated with coronary heart disease risk. We therefore hypothesized that variation in PON1 and PON2 genes may be associated with variation in birth weight. This relationship was examined in 90 consecutive Trinidadian neonates of different ethnic origins. We found that variation in PON2 was significantly associated with variation in birth weight in Trinidadian neonates of south Asian origin. Among the neonates of South Asian origin, those who were homozygous for PON A148/A148 had significantly lower birth weight, by approximately 00 g, compared with those with the other two genotypes (P < 0.05). For neonates of south Asian origin, PON2 A148/A148 homozygotes were significantly more prevalent in those comprising the lowest tertile for birth weight than those comprising the highest tertile (0.41 versus 0.24, P < 0.05). There were no significant associations of PON variation with any phenotype in other ethnic groups. We conclude that among neonates of South Asian origin, homozygosity for PON2 A148/A148, is associated with significantly lower birth weight. This suggests that genetic factors in the fetus may be important determinants of neonatal birth weight and possibly of more distal adult phenotypes, such as coronary heart disease.(AU)

Estimating African American admixture proportions by use of population-specific alleles

We analyzed the European genetic contribution to 10 populations of Africans descent in the United States (Maywood, Illinois; Detroit; New York; Philadelphia; Pittsburgh; Baltimore; Charleston, South Carolina; New Orleans; and Houston) and in Jamaica, using nine autosomal DNA markers. These markers either are population-specific or show frequency differences >45 percent between the parental populations and are thus especially informative for admixture. European genetic ancestry ranged from 6.8 percent (Jamaica) to 22.5 percent (New Orleans). The unique utility of these markers is reflected in the low variance associated with these admixture estimates (SEM 1.3 percent -2.7 percent). We also estimated the male and female European contribution to African Americans. on the basis of informative mtDNA (haplogroups H and L) and Y Alu polymorphic markers. Results indicate a sex-biased gene flow from Europeans, the male contribution being substantially greater that the female contribution. mtDNA haplogroups analysis shows no evidence of a significant maternal Amerindian contribution to any of the 10 populations. We detected significant nonrandom association between two markers located 22 cM apart (FY-null and AT3), most likely due to admixture linkage disequilibrium created in the interbreeding of the two parental populations. The strength of this association and the substantial genetic distance between FY and AT3 emphasize the importance of admixed populations as a useful resources for mapping traits with different prevalence in two parental populations (AU)

The Trp64 A rg mutation of the B3- Adrenergic Receptor Is associated with hyperglycemia and current body mass index in Jamaican women

The Trp64Arg mutation the the beta3-adrenergic receptor (beta3-AR) has been linked to earlier onset of non-insulin-dependent diabetes mellitus (NIDDM), insulin resistance, abdominal obesity, and an increase capacity to gain weight in some European and Japanese populations. We studied the prevalence of the mutation and its association with NIDDM and obesity in our population, in which both rates are high, especially in women. The frequency of the homozygous mutation was 1.53 percent, and of the Arg allele, 10.5 percent. Rates were similar in men and women. Significantly higher body mass index (BMI), weight, hip circumference, and fasting and postchallenge 2 hour blood glucose concentrations were associated with the presence of the Arg allele in women but not in men. The association with weight and hip measurements and with hyperglycemia was present only in women aged less than 55 years. In multivariate analysis, the mutation was associated with the BMI and sex in a model that also included age. The variation in fasting and 2 hour blood glucose levels were predicted by beta3-AR, gender, age and BMI. These results suggest that the presence of the mutation contributes to obesity and hyperglycemia in our female population.(AU)

Statistical analysis of data for three British ethnic groups from a new STR multiplex

Data have been collected from 602 Caucasians, 190 Afro-Caribbeans and 257 Asians of Indo/Pakistani descent who have been profiled using a new six locus short tandem repeat (STR) multiplex. The data have been analysed by conventional significance testing methods: the exact test, homozygosity, and conventional goodness of fit to Hardy-Weinberg proportions. Frequency tables are given and the expected performance in British forensic casework is discussed.(AU)

Distribution of HLA and haplotypes of Colombian and Jamaican black populations

To investigate the genetic background of the black populations of Colombia and Jamaica, we determined HLA types of 78 Colombian and 98 Jamaican blacks from 2 different socioeconomic groups (Jamaican #1 and Jamaican #2) and estimated the frequencies of HLA genes and haplotypes. A phylogenetic tree based on the HLA gene frequencies revealed that Jamaican #1 and Jamaican #2 were distinct from each other, Jamaican #1 being closely related to Colombian blacks and the Jamaican #2 being closely related to Senegalese and Zairean populations. Three-locus haplotypes of Colombian and Jamaican #1 blacks were an admixture between Africans and Caucasians or South American Indians while Jamaican #2 blacks were relatively homogeneous and appeared to conserve African lineages. The major five-locus HLA haplotypes were not shared among Colombian, Jamaican #1 and Jamaican #2 blacks. These results indicated that the black populations of Colombia and Jamaica were originated from African blacks and admixed variably with Caucasians and South Americans Indians to make genetic subpopulations in Colombia and Jamaica. (AU)

Myasthenia gravis and HLA phenotypes in Jamaicans

We determined HLA-antigen frequencies and corresponding relative risks (RR) in 30 Jamaicans with myasthenia gravis (MG) and 40 normal controls.. using a microcytotoxicity assay and commercially prepared typing trays, we found that the strongest HLA associations with MG in Jamaicans were with HLA-A2 (RR = 6.15), HLA-B8 (RR = 3.4), HLA-B13 (RR=7.6), and DQw4 (RR = 3.8). After correction of the P value for the number of antigens tested, only HLA-A2 was stastistically significantly increased in MG patients. There was a statistically significant negative association between Mg and HLA-DR2, as well as as HLA-A9 and -B5. No correlation was observed between HLA phenotype, thymic disease, clinical grades, or disease course. HLA-A2 and sex were independent risk factors for MG, female patients having a higher risk (RR = 5.8). Further studies using larger patient and control groups, locally derived typing sera, and DNA probe analysis are indicated. (AU)

Blood group frequencies of the population of Trinidad and Tobago, West Indies

The results of grouping tests performed on blood samples collected over a five-year period at the Trinidad and Tobago Forensic Science Centre are presented. The samples were tested using the ABO, PGM, EAP and GLO blood group systems. Phenotypic frequencies and allele frequencies for each system were calculated for the two major ethnic groups of the population, the African and East Indian. Matching probabilities, which can be used in the interpretation of physical evidence in forensic cases, were also calculated. (AU)

HLA-DQA1 and DQB1 Alleles associated with genetic susceptibility to IDDM in a black population

Transracial analysis provides a method of distinguishing primary associations between insulin-dependent diabetes mellitus (IDDM) and HLA class II alleles from those secondary to linkage disequilibrium. Blacks show DR-DQ relationships that are different from other races and are a useful group in which to investigate HLA-D region associations with IDDM. In this study, the frequencies of HLA-DQA1 and -DQB1 alleles in Afro-Caribbean IDDM and control subjects were compared. Alleles were identified with sequence-specific oligonucleotide probing. The DQA1 allele A3 was positively associated with IDDM (relative risk[RR] = 25.3, corrected P [Pc]<7.0 x 10 -6). THe DQB1 alleles DQw2 and DQw8 were also positively associated (RR = 4.7, Pc<6.5 x 10 -3 and RR = 12.3,Pc = 3.4 x 10 -3, respectively). The A1.2 and DQw6 alleles were negatively associated (RR = 0.16, Pc<3.5 x 10 -3 and RR = 0.15, Pc = 2.4 x 10 -2, respectively). These findings were compared to data from other races. The positive associations with A3 and DQw2 are consistent with all racial groups investigated. The negative association with DQw6 is present in all racial groups in which it is a common allele. These findings suggest that DQ alleles, and hence DQ molecules, may directly affect predisposition to IDDM. (AU)

Genealogical and genetical African admixture estimations, blood pressure and hypertension in a Caribbean community

This study examines the relationships between blood pressure, prevalence of hypertension, and the degree of black African admixture in the population of the Caribbean Island of La Desirade which is homogenous with respect to the environmental factors and for which the socioeconomical stratification does not match racial origin. The degree of admixture was estimated by using both genealogical information and genetic markers. Blood pressure was repeatedly measured using an automatic sphygmomanometer. After adjustment for age, sex, ponderal index, Na/K urinary ratio, and clinical alcoholism, blood pressure and prevalence of hypertension were found to be significantly higher for the individuals having the largest proportion of genes of black origin. Identical results were obtained when either genetic markers or genealogical information were used as an individual-estimator of admixture. (AU)

Studies on an isolated West Indies population: IV. Genetic study of hearing loss

Hearing troubles were found to be very frequent among inhabitants of French origin in a small Caribbean island. Segregation analysis of hearing loss was performed in 165 complete nuclear families and revealed that familial aggregation could be entirely explained by a single recessive gene with high frequency (0.40). Homozygous individuals for this gene would probably be more suscepticle to ototoxic agents than other individuals. High frequency of this gene may be due to a founder effect (AU)

Neonatal screening for sickle cell disease in the Eastern Province of Saudi Arabia

Neonatal screening for sickle cell disease has been established in three hospitals in the Eastern Province of Saudi Arabia. In the first 17 months of this programme, 5630 cord blood samples were screened with the detection of 47 babies with an FS phenotype. The sickle cell trait occurred in 4.4 percent births at Al Khobar, in 6.7 percent in Dammam and in 17.9 percent in Qatif. An apparent excess of the FS phenotype over that predicted from the observed S gene frequency occurred at all three centres. The cause of this excess remains unknown although a high prevalence of sickle cell-beta-o thalassaemia and the effects of non-random mating may be contributory factors. (Summary)

Cord blood screening for sickle hemoglobin: evidence against a female preponderance of hemoglobin S

The genes controlling á-chain synthesis in hemoglobins A, S, and C are not sex linked, and sex differences in the prevalence at birth of the various á-chain genotypes would not be expected. However, the results of a recent study in the United States appeared to conflict with this expectation. In a series of 3,976 black infants whose cord blood was examined by hemoglobin electrophoresis, electrophoretic patterns compatible with AS and SS genotypes occurred in significantly higher proportions of females than males. Moreover, the number of SS births was significantly higher than expected on the basis of the observed frequency of S genes. A similar, but much larger screening program is in progress in Jamaica; results for the first 70,000 births are presented below. There were no appreciable sex differences in the proportions with AS and SS genotypes, and the number of SS births was not significantly in excess of its expected value. It seems likely, therefore, that the findings reported previously were the result of stochastic variation. (AU)

A theoretical note on sex linkage and race differences in spatial visualization ability

Evidence on the poorer spatial visualization ability in various Negro populations compared to the white populations and the direction and magnitude of sex differences in spatial ability relative to other abilities suggests the genetic hypothesis that spatial ability is enhanced by a sex-linked recessive gene and that, since the 20-30 percent admixture of Caucasian genes in American Negroes came mostly from male white ancestors, relatively fewer X-linked than autosomal Caucasian genes were transmitted to the American Negro gene pool. The genetic model as explicitly formulated indicates the kinds of data which could substantiate or disprove the theory, but which do not now exist (AU)

Screening cord bloods for detection of sickle cell disease in Jamaica

A cord-blood screening program, designed primarily for detecting sickle cell disease, has been in operation for seven months (8 000 samples) at a large maternity unit in Kingston, Jamaica. We describe techniques of cord-blood collection and electrophoretic investigation on both cellulose acetate and agar gel. These methods appear to give rapid, valid results at minimal expense and are well adapted to screening large populations (AU)