HIV-Infection,Atherosclerosis and the Inflammatory Pathway: Candidate Gene Study in a Spanish HIV-Infected Population

Background

Higher prevalence of atherosclerosis and higher cardiovascular risk is observed in HIV-infected individuals. The biological mechanisms underlying these processes are unclear. Several studies have implicated genetic variants in the inflammatory genes in cardiovascular disease and in HIV natural course infection.

Methods & Findings

In this study we have tested the possible association between genetic variants in several inflammatory genes and asymptomatic cardiovascular disease measured by carotid intima media thickness (cIMT) and atherosclerotic plaque presence as dependent variables in 213 HIV-infected individuals. A total of 101 genetic variants in 25 candidate genes have been genotyped. Results were analyzed using Plink and SPSS statistical packages. We have found several polymorphisms in the genes ALOX5 (rs2115819 p = 0.009), ALOX5AP (rs9578196 p = 0.007; rs4769873 p = 0.004 and rs9315051 p = 0.0004), CX3CL1 (rs4151117 p = 0.040 and rs614230 p = 0.015) and CCL5 (rs3817655 p = 0.018 and rs2107538 p = 0.018) associated with atherosclerotic plaque. cIMT mean has been associated with CRP (1130864 p = 0.0003 and rs1800947 p = 0.008), IL1RN (rs380092 p = 0.002) and ALOX5AP (rs3885907 p = 0.02) genetic variants.

Conclusions

In this study we have found modest associations between genetic variants in several inflammatory genes and atherosclerotic plaque or cIMT. Nevertheless, our study adds evidence to the association between inflammatory pathway genetic variants and the atherosclerotic disease in HIV-infected individuals.     

Differences in the expression of the ASIP gene are involved in the recessive black coat colour pattern in sheep: evidence from the rare Xalda sheep breed

Here we have tested the hypothesis of association between different levels of agouti signalling peptide (ASIP) mRNA and the recessive black coat colour in the rare Xalda breed of sheep. To deal with this task, we first tested the possible action of both the dominant black extension allele (E(D)) and a 5-bp deletion (X99692:c.100_104del; A(del)) in the ovine ASIP coding sequence on the black coat colour pattern in 188 Xalda individuals. The E(D) allele was not present in the sample and only 11 individuals were homozygous for the A(del)ASIP allele. All Xalda individuals carrying the A(del)/A(del) genotype were phenotypically black. However, most black-coated individuals (109 out of 120) were not homozygous for the 5-bp deletion, thus rejecting the A(del)/A(del) genotype as the sole cause of recessive black coat colour in sheep. Differences in expression of ASIP mRNA were assessed via RT-PCR in 14 black-coated and 10 white-coated Xalda individuals showing different ASIP genotypes (A(wt)/A(wt), A(wt)/A(del) and A(del)/A(del)). Levels of expression in black animals were significantly (P < 0.0001) lower than those assessed for white-coated individuals. However, the ASIP genotype did not influence the ASIP mRNA level of expression. The consistency of these findings with those recently reported in humans is discussed, and the need to isolate the promoter region of ovine ASIP to obtain further evidence for a role of ASIP in recessive black ovine pigmentation is pointed out.     

Multivariate characterization of morphological traits in Burkina Faso sheep

A total of 6440 female sheep from Burkina Faso were scored for seven body measurements and four qualitative morphological traits. Sampling included the three main environmental areas and sheep breeds of Burkina Faso: the Sahel area (Burkina-Sahel sheep), the Sudan-Sahel area (Mossi sheep) and the Sudan area (Djallonké sheep). Canonical analyses showed that differences in body measurements between the Sudan and the Sudan-Sahel sheep were small even though most body traits showed higher average values in the Burkina-Sahel sheep: the shortest Mahalanobis distance was found between the Sudan and the Sudan-Sahel populations (1.54), whilst that between the Sudan and the Sahelian populations was the largest (7.88). Discriminant analysis showed that most Sudan (Djallonké) individuals (60.85%) were classified as Sudan-Sahel (Mossi) individuals whilst most Burkina-Sahel individuals were classified into their environmental area of sampling (89.46%). Correspondence analyses indicated that the Burkina-Sahel sheep population clustered together with dropping ears, black and brown colour patterns and presence of wattles, the Sudan sheep were closely associated with long hair and vertical and curled ears and that the Sudan-Sahel sheep did not have clear associations with qualitative phenotypic traits. At the morphological level, the Sudan-Sahel (Mossi) sheep population can be considered a geographical subpopulation belonging to the Djallonké breed, showing some particularities, namely larger body size, due to the particular environmental condition of the area in which it is managed and a continuous gene flow from Sahelian sheep, The information reported in this study will be the basis for the establishment of further characterization, conservation and selection strategies for Burkina Faso sheep.     

Molecular definition of an allelic series of mutations disrupting the myostatin function and causing double-muscling in cattle

We have determined the entire myostatin coding sequence for 32 double-muscled cattle sampled from ten European cattle breeds. Seven DNA sequence polymorphisms were identified, of which five would be predicted to disrupt the function of the protein, one is a conservative amino acid substitution, and one a silent DNA sequence variant. Four additional DNA sequence polymorphisms were identified in myostatin intronic sequences. In all but two breeds, all double-muscled animals were either homozygous or compound heterozygotes for one of the five loss-of-function mutations. The absence of obvious loss-of-function mutations in the coding sequence of the two remaining breeds points either towards additional mutations in unexplored segments of the gene, or towards locus heterogeneity of double-muscling. Received: 20 September 1997 / Accepted: 11 October 1997     

Fast-germinating low β-glucan mutants induced in barley with improved malting quality and yield

Summary Mutation breeding has been used to improve the speed of germination in the high-yielding spring barley variety Troubadour. Five mutants were selected which combined fast germination and good agronomic performance. Two of these mutants yielded significantly more than did Troubadour over eight environments, and showed a clear improvement in their malting quality through an increase in extract yield. The improvement in malting quality appeared to be due to a decrease in the -glucan content, which seemed to enhance the germination speed and thus the starch degradation. The improvement in grain yield is postulated to be due to a better early growth caused by the enhanced germination speed. All the described changes could theoretically be explained by a single mutation event in each of the mutant genotypes, affecting the quantity of -glucans present in the endosperm.     

Cis- and trans-titanium complexes with doubly silyl-bridged dicyclopentadienyl ligands: molecular structure of [(TiCl)2(μ-O){(SiMe2)2(η-C5H3)2}]2(μ-O)2

The reaction of TiCl₄ with Li₂[(SiMe₂)₂(η⁵-C₅H₃)₂] in toluene at room temperature afforded a mixture of cis- and trans-[(TiCl₃)₂{(SiMe₂)₂(η⁵-C₅H₃)₂}] in a molar ratio of 1/2 after recrystallization. The complex trans-[(TiCl₃)₂{(SiMe₂)₂(η⁵-C₅H₃)₂}] was hydrolyzed immediately by the addition of water to THF solutions to give trans-[(TiCl₂)₂(μ-O){(SiMe₂)₂(η⁵-C₅H₃)₂}] as a solid insoluble in all organic solvents, whereas hydrolysis of cis-[(TiCl₃)₂{(SiMe₂)₂(η⁵-C₅H₃)₂}] under different conditions led to the dinuclear μ-oxo complex cis-[(TiCl₂)₂)(μ-O){(SiMe₂)₂(η⁵-C₅H₃)₂}] and two oxo complexes of the same stoichiometry [(TiCl)₂(μ-O){(SiMe₂)₂(η⁵-C₅H₃)₂}]₂(μ-O)₂ as crystalline solids. Alkylation of cis- and trans-[(TiCl₃)₂{(SiMe₂)₂(η⁵-C₅H₃)₂}] with MgCIMe led respectively to the partially alkylated cis-[(TiMe₂Cl)₂{(SiMe₂)₂(η⁵-C₅H₃)₂}] and the totally alkylated trans-[(TiMe₃)₂{(SiMe₂)₂(η⁵-C₅H₃)₂}] compounds. The crystal and molecular structure of the tetranuclear oxo complex [(TiCl)₂(μ-O){(SiMe₂)₂(η⁵-C₅H₃)₂}]₂(μ-O)₂ was determined by X-ray diffraction.