French Caucasians Research Articles

Genetic studies of the sulfonylurea receptor gene locus in NIDDM and in morbid obesity among French Caucasians.

The sulfonylurea receptor (SUR) is a key component in glucose-stimulated insulin secretion. Obesity and NIDDM are frequently associated and share some metabolic abnormalities, suggesting that they might also share some susceptibility genes. Thus, the SUR encoding gene is a plausible candidate for a primary pancreatic beta-cell defect and thus for hyperglycemia and weight gain. Through association and linkage studies, we have investigated the potential role of the SUR gene in families with NIDDM and in two independent sets of morbidly obese families. The exon 22 T-allele at codon 761 was more common in patients with NIDDM (7.7%) and morbid obesity (7.8%) than in control subjects (1.8%, P = 0.030 and P = 0.023, respectively). This variant was associated with morbid obesity (odds ratio 3.71, P = 0.017) and NIDDM (odds ratio 2.20, P = 0.04; association dependent on BMI). Although the frequencies for intron 24 variant were similar in all groups, morbidly obese patients homozygous for the c-allele had a more deleterious form of obesity. Sib-pair linkage studies with NIDDM in French Caucasian families gave no evidence for linkage to the SUR locus. However, in one set of the obese families, we found an indication for linkage with a SUR-linked microsatellite marker (D11S419, P = 0.0032). We conclude that in Caucasians, the SUR locus may contribute to the genetic susceptibility to NIDDM and obesity.

Glutathione S-transferase class ? in French alcoholic cirrhotic patients

The lack of glutathione S-transferase mu (GST mu) was examined in 45 healthy French Caucasians and 45 alcoholic cirrhotic French Caucasians: microsamples of blood were taken and DNA amplified by the polymerase chain reaction. We have concluded that there is no relationship between this genotype and the development of alcoholic cirrhosis in these heavy consumers of ethanol.

Phenotyping polymorphic drug metabolism in the French Caucasian population

Because of the large interethnic differences in the incidence of poor metabolizer phenotypes, French Caucasians have been studied for two independent polymorphisms, debrisoquine/dextromethorphan and mephenytoin metabolism. One hundred and thirty-two unrelated French Caucasians were phenotyped using oral doses of dextromethorphan 20 mg and mephenytoin 100 mg. Individual dextrorphan excretion over 8 h and the dextromethorphan/dextrorphan metabolic ratio were calculated. Extensive metabolizers were taken as subjects with a high dextrorphan output (15.56 mumol/8 h) and a low metabolic ratio (0.0023), and poor metabolizers were those with a low dextrorphan output (0.39 mumol/8 h) and a high metabolic ratio (7.00). Individual 4-hydroxymephenytoin excretion and mephenytoin hydroxylation indices were also determined. Extensive metabolizers eliminated large amounts of 4 hydroxymephenytoin (133.2 mumol/8 h) and had a hydroxylation index of 1.99, and poor metabolizers, because of impaired mephenytoin metabolism, had a high hydroxylation index (277). The incidence of the poor metabolizer phenotype was 3% for dextromethorphan (95% confidence limits 0.5%-8.5%) and 6% for mephenytoin (95% confidence limits 2%-12.5%).

T cell activation via CD2 [T, gp50] molecules: accessory cells are required to trigger T cell activation via CD2-D66 plus CD2-9.6/T11(1) epitopes.

Abstract Binding monoclonal antibodies (MAb) both to D66 and 9.6/T11(1) epitopes on the CD2 [T,gp50]-defined molecule produces a high level of T cell mitosis. This was observed with a battery of MAb of different isotypes. In contrast, none of the anti-D66 or anti-9.6/T11(1)Ab could trigger T cell proliferation in combination with anti-T11(3). Moreover, all anti-D66-9.6/T11(1) pairs of MAb tested required monocytes to activate T cells which were recruited through their Fc receptors. Variations among normal individuals were observed in the level of response to anti-D66-9.6/T11(1) pairs of Ab, 75% of a population of French Caucasians giving a high response. The level of response of a given individual was determined by his accessory cells. However, the level of response of an individual appeared to be minimally influenced by the isotype of a peculiar anti-D66 or anti-9.6/T11(1) Ab. The addition of exogeneous IL 2 could overcome the removal of accessory cells or the modulation of CD3 molecules. In contrast, IL 2 receptor appearance was not overcome by removal of monocytes. Thus, T cell activation via CD2 seems to be produced by "touching" several definite regions of this molecule which trigger a cascade of events similar to those produced by mitogenic lectins. One can assume that the appropriate conformational changes of the CD2 molecule induced by anti-D66-9.6/T11(1) pairs of Ab are solely produced when they are presented by accessory cells. This leaves open the question of whether accessory cells would also play a more active role.

HLA and longevity.

One hundred fifty-five healthy nonagenarians, 45 men and 100 women, all French Caucasians, were phenotyped for alleles of the A, B, C, DR loci of the HLA complex. The observed HLA antigen frequencies were compared to those of a control series of 133 males and 179 females whose ages ranged from 10 to 50 years. When comparing the total young and elderly series, no significant differences were observed with respect to HLA antigen distribution or heterozygosity at any of the loci. When taking sex difference into account, however, an excess of the Cw1 antigen was found in the group of elderly females (p less than 0.001) and an excess of the Cw7 antigen in the group of elderly males (p less than 0.001). Of particular significance was the fact that Cw7 belonged in this instance to a phenotypic combination (and most probably to the corresponding haplotype) A1/Cw7/B8/DR3 which was found significantly increased in male nonagenarians (p less than 0.001). These results support the hypothesis that certain HLA haplotypes are associated with survival advantage.

HEAT REACTIONS OF CAUCASIANS IN TEMPERATE, IN HOT, DRY, AND IN HOT, HUMID CLIMATES.

Heat reactions of Australian Caucasians living in hot, humid climates and of French Caucasians living in hot, dry climates were compared to unacclimatized and highly acclimatized male Caucasians living in Johannesburg. The experiments were conducted in climatic chambers at temperatures of 90 F wet-bulb and 93 F dry-bulb, and a workload of 1 liter O2/min consumption. The Australians did not differ significantly from the French in the three reactions to heat, except for a slightly significantly higher sweat rate in the 1st hr. The French and Australians had lower mean rectal temperatures and heart rates and higher sweat rates than the unacclimatized South Africans. Although the trend is toward a significant difference for all hours, the differences are not always significant. Living and working in the hot, humid tropics and in the hot, dry desert evidently confers a certain measure of acclimatization to heat. Quantitatively this can be expressed as 50% of the difference between unacclimatized and acclimatized men. This is, however, considerably less than the condition achieved by systematic artificial acclimatization. Australian versus French Caucasians in heat reactions; effects of various climates on Caucasians; heat reactions in the desert; heat reactions in the tropics; physiological effects of hot, dry and hot, humid climates Submitted on August 19, 1963