We designed an association (retrospective, case control) study aimed at evaluating associations between genetic variations of the human apolipoprotein B (apoB) gene and clinical diagnosis of essential hypertension Our approach was to compare the distribution of the alleles of a highly polymorphic variable number of tandem repeats localized 3' to the human apoB gene, the apoB 3' hypervariable region (HVR), in a group of normotensive and a group of hypertensive individuals We collected DNA samples from 437 unrelated nationals (215 normotensives and 222 hypertensives) from the United Arab Emirates (UAEs), and we determined their apoB 3' HVR allele and genotype status with a polymerase chain reaction-based assay In the UAE population, we found 18 alleles underlying a total of 51 genotypes The distribution of these alleles was significantly different between normotensive and hypertensive UAE nationals The main peak of the distributions occurred at 35 repeats among hypertensives (with a relative frequency of 257% versus 196% in normotensives) and at 37 repeats among normotensives (288% versus 203% in hypertensives) Alleles with 21, 23, 25, 49, and 55 repeats were found in hypertensives only (with a combined relative frequency of 76%) We conclude that variations of the apoB gene, or of a nearby gene, that may be in linkage disequilibrium with these alleles play a role in the development of essential hypertension in the UAEs

Association of an Apolipoprotein B Gene Marker With Essential Hypertension

Background
Apolipoprotein (Apo) B is the major component of low-density lipoprotein (LDL), very low-density lipoprotein (VLDL) and chylomicrons. Many genetic polymorphisms of the Apo B have been described, associated with variation of lipid levels. However, very few studies have evaluated the effect of the variable number of tandem repeats region 3' of the Apo B gene (3'APOB-VNTR) polymorphism on the lipid profiles in the special minority subgroups in China. Thus, the present study was undertaken to study the effect of the 3'APOB-VNTR polymorphism on the serum lipid levels in the Guangxi Hei Yi Zhuang and Han populations.

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Effect of the 3'APOB-VNTR polymorphism on the lipid profiles in the Guangxi Hei Yi Zhuang and Han populations

ApoB 3′ ′ hyper variable region (ApoB 3′HVR) is highly polymorphic and hence an informative marker. It could be an ideal candidate to study the genetic heterogen eity among different population groups of the Indian subcontinent. It is one of the markers for which popu lation data are available. This makes the ApoB 3′HVR an ideal locus for a pilot study to investigate the rel ationships between different populations and the microevolutionary processes leading to their present-day distribution. In the present investigation, we have stu died ApoB 3′HVR in three endogamous groups of North India and have compared these populations on the basis of inter- and intra-group diversity. The sub-populations chosen were Bhargavas, Chaturvedis, and non-Bhargava non-Chaturvedi Brahmins of Uttar Pradesh. Nineteen segregating alleles were detected in our population groups. The average observed heterozygosity was quite high (0.717), suggesting high diversity at the ApoB 3′HVR locus. Low value of a verage GST (0.0126) and FST (0.002) reflects non-significant deviation of heterozygosity between the three subgroups. On comparing the three study groups with ApoB 3′HVR of other Indian and world populations, it was clear that grea ter diversity was observed for Africans followed by Europeans and Asians. There was relative homogeneity among the continental groups. In our study it was observed that there was high heterozygosity, an e xtended range of allele size, a quasi un imodal allele size distribution, centred on HVE 37. These findings indicate that our populations may be characterized as ancestral, since similar features are observed in the African population. ApoB 3′HVR polymorphism suggests that despite practising restricted marital patterns, these groups or castes do not significantly differ from each other at the genetic level. This may be b ecause of the fact that divergence time may not be enough to cause genetic variation in these groups. However, it may not be ruled out that the ApoB 3′HVR polymorphism probably predates the divergence of these sub-castes. We are further testing this observation, using mt -DNA for maternal lineages and Y-chromosome markers for paternal lineages.

Genetic variation of ApoB 3' hyper variable region polymorphism among Brahmins of North India

L‘apolipoproteine B (apo B) est le composant proteique principal des LDL, des VLDL et des chylomicrons. De nombreux polymorphismes du gene de l‘apolipoproteine B ont ete rapportes. En particulier, un polymorphisme d‘insertion\deletion situe dans la partie codante du peptide signal de l‘apo B est associe a des modifications de concentrations lipidiques et du risque cardiovasculaire dans la population generale. Les dyslipoproteinemies sont frequentes au cours de l‘obesite. Le but de notre travail etait d‘etudier les effets du polymorphisme d‘insertion\deletion du gene de l‘apo B sur les lipides des sujets obeses ; 234 sujets obeses non apparentes (74 hommes et 160 femmes, âges de : 39,3 ± 10,5 ; indice de masse corporelle (IMC) : 32,8 ± 4,7) ont ete recrutes. Le polymorphisme insertion\deletion etait determine par electrophorese sur gel de polyacrylamide apres amplification de l‘ADN par PCR. Les frequences alleliques etaient de 0,71 pour l‘insertion et 0,29 pour la deletion. Ces frequences sont comparables a celles trouvees dans les populations caucasiennes. Dans la population totale, on observe chez les homozygotes pour la deletion (del\del) une augmentation significative du rapport cholesterol‐total\cholesterol‐HDL (p ∓ 0,004), du rapport cholesterol‐LDL\cholesterol‐HDL (p ∓ 0,01) et des TG‐VLDL (p ∓ 0,05). Chez ces memes sujets, on note egalement une tendance a l‘augmentation des triglycerides (p ∓ 0,09) et une tendance a la baisse du cholesterol‐HDL, de l‘apolipoproteine AI et de la fraction LpAI. La deletion entraine l‘absence de 3 acides amines (Leu‐Ala‐Leu) dans le peptide signal de l‘apo B. Chez les sujets obeses, ces changements de structure pourraient retentir sur le metabolisme des lipoproteines et entrainer ainsi des variations des concentrations lipidiques.

Polymorphisme insertion\délétion du gène de l‘apolipoprotéine B : effet sur les concentrations lipidiques chez les sujets obèses

Apo B 3’ hyper variable region (Apo B 3’ HVR) is a highly polymorphic and hence an informative marker. It could be an ideal candidate to study the genetic heterogeneity among different population groups of Indian subcontinent. It is one of the marker for which numerous population data is available. This makes Apo B 3’HVR an ideal locus for a pilot study to investigate the relationships between different populations and the micro-evolutionary processes leading to their present day distribution. In the present study, we have studied ApoB3’HVR among North Indians and South Indians and have compared these populations on the basis of within group and between group diversity. For this purpose we have selected 600 North Indians and 200 South Indians at random. Total 21 segregating alleles were detected in our population groups. The average observed heterozygosity was quite high (avg.0.753) suggesting high diversity at ApoB’3HVR locus. Low value of average Gst (0.0005) and Fst (0.035) reflects non-significant deviation of heterozygosity between the two groups. On comparing our study populations with central Indian non tribal and tribal groups, it was found that there is relative homogeneity among the three non tribal groups and on computing genetic distances between the four groups, it was observed that tribal significantly differ from the three non-tribal groups. On comparing with other world populations grouped in continental groups, it was clear that greater diversity was observed for Africans followed by the Europeans and Asians. There was relative homogeneity among the continental groups. North Indians and South Indians were found closure to the Asians while non tribal Central Indians clustered with the Eurpeans. We are further testing these observations, by incorporating more realistic demographic models and by using mt-DNA for maternal lineages and Y-chromosome markers for paternal lineages.

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S Wang

Papers

The association of polymorphisms at a VNTR locus 3' to the apolipoprotein B gene with coronary heart disease in Chinese population.