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Association of gene polymorphism with serum levels of inflammatory and angiogenic factors in Pakistani patients with age-related macular degeneration.

Ambreen F, Ismail M, Qureshi IZ - Mol. Vis. (2015)

Bottom Line: For rs1800795, patients with the GG genotype showed significantly raised levels of IL-6 compared to those with GC and CC genotypes (p<0.0001).Serum IL-8 levels were significantly higher in patients with the GG genotype compared to the GC and CC genotypes for the single nucleotide polymorphism (SNP) rs2227543 (p<0.002).Similarly, significantly higher VEGF levels were detected for genotype TT for rs3025039 SNP (p<0.038).

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Animal and Human Physiology, Quaid-i-Azam University, Islamabad, Pakistan.

ABSTRACT

Purpose: To study the association of serum levels of inflammatory mediators and angiogenic factors with genetic polymorphism in Pakistani age-related macular degeneration (AMD) patients.

Methods: This was a cross-sectional and case-control study that included 90 AMD patients diagnosed through slit-lamp examination, fundoscopy, and ocular coherence tomography. For reference and comparison purposes, 100 healthy age-matched subjects (controls) were also recruited. IL-6, IL-8, VEGF, and CRP levels were estimated in the serum samples of patients and control subjects. Using restriction fragment length polymorphism, single nucleotide polymorphisms were studied in IL-6 (rs1800795, rs1800796, rs1800797), IL-8 (rs4073, rs2227306, rs2227543), VEGF (rs3025039, rs699947), and CRP genes (rs1205, rs1130864). Since the data were obtained from a sample population, the Box-Cox transformation algorithm was applied to reduce heterogeneity of error. Multivariate analyses of variance (M-ANOVA) were applied on the transformed data to investigate the association of serum levels of IL-6, IL-8, VEGF, and CRP with AMD. Genotype and allele frequencies were compared through χ(2) tests applying Hardy-Weinberg equilibrium. The serum concentrations of IL-6 and IL-8, VEGF, and CRP between homozygotes and heterozygotes were compared through one-way ANOVA. Significance level was p<0.05.

Results: Compared to control subjects, serum IL-6 (p<0.0001), IL-8 (p<0.0001), VEGF (p<0.0001), and CRP (p<0.0001) levels were significantly elevated in the AMD patients. For rs1800795, patients with the GG genotype showed significantly raised levels of IL-6 compared to those with GC and CC genotypes (p<0.0001). Serum IL-8 levels were significantly higher in patients with the GG genotype compared to the GC and CC genotypes for the single nucleotide polymorphism (SNP) rs2227543 (p<0.002). Similarly, significantly higher VEGF levels were detected for genotype TT for rs3025039 SNP (p<0.038). However, no significant alteration in serum CRP levels was detected in hetero- or homozygotes for rs1205 and rs1130864 SNPs.

Conclusions: Serum IL-6, IL-8, and VEGF levels are substantially increased in AMD, and the levels coincide with polymorphism in the respective gene. No such relationship appears to exist with regard to SNPs of CRP.

No MeSH data available.


Related in: MedlinePlus

The box-and-whisker plot represents the mean and minimum to maximum range of IL-6, IL-8, VEGF and CRP levels in transformed data. Serum levels were measured in 100 control subjects and 90 AMD patients. Among AMD patients 63 had wet type and 27 had dry type AMD. The serum levels of (A) IL-6, (B) IL-8, (C) VEGF and (D) CRP were significantly elevated in AMD patients compared to control subjects (p<0.0001). The levels of (A) IL-6 and (B) IL-8 were significantly elevated in dry AMD patients compared to wet AMD patients. The levels of (C) VEGF and (D) CRP were significantly elevated in wet AMD patients compared to dry AMD patients (p<0.0001).
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f1: The box-and-whisker plot represents the mean and minimum to maximum range of IL-6, IL-8, VEGF and CRP levels in transformed data. Serum levels were measured in 100 control subjects and 90 AMD patients. Among AMD patients 63 had wet type and 27 had dry type AMD. The serum levels of (A) IL-6, (B) IL-8, (C) VEGF and (D) CRP were significantly elevated in AMD patients compared to control subjects (p<0.0001). The levels of (A) IL-6 and (B) IL-8 were significantly elevated in dry AMD patients compared to wet AMD patients. The levels of (C) VEGF and (D) CRP were significantly elevated in wet AMD patients compared to dry AMD patients (p<0.0001).

Mentions: The ANOVA for λ= 0.413 that yielded the lowest error sums of squares was used for hypothesis testing. M-ANOVA showed that serum levels of IL-6, IL-8, VEGF and CRP were significantly elevated in AMD patients (p<0.0001; Wilk’s λ = 0.064; F= 278.7); however, these levels were not found to be associated with gender (p<0.560; Wilk’s λ = 0.997; F= 0.463). The levels of all these factors were found significantly associated with the type of AMD that is wet or dry (p<0.0001; Wilk’s λ = 0.018; F= 147.406). IL-6 and IL-8 levels were significantly increased in patients with dry AMD (p<0.0001), while serum VEGF and CRP levels were significantly elevated in patients with wet AMD (p<0.0001; Figure 1A-D). There was no significant difference in the serum levels of inflammatory factors with respect to age groups (p>0.705; Wilk’s λ = 0.983; F=0.631; Table 3). No significant change was observed in the concentration of IL-6, IL-8, VEGF, and CRP with respect to the pattern of AMD (p<0.302; Wilk’s λ = 0.882; F=1.202; Table 4).


Association of gene polymorphism with serum levels of inflammatory and angiogenic factors in Pakistani patients with age-related macular degeneration.

Ambreen F, Ismail M, Qureshi IZ - Mol. Vis. (2015)

The box-and-whisker plot represents the mean and minimum to maximum range of IL-6, IL-8, VEGF and CRP levels in transformed data. Serum levels were measured in 100 control subjects and 90 AMD patients. Among AMD patients 63 had wet type and 27 had dry type AMD. The serum levels of (A) IL-6, (B) IL-8, (C) VEGF and (D) CRP were significantly elevated in AMD patients compared to control subjects (p<0.0001). The levels of (A) IL-6 and (B) IL-8 were significantly elevated in dry AMD patients compared to wet AMD patients. The levels of (C) VEGF and (D) CRP were significantly elevated in wet AMD patients compared to dry AMD patients (p<0.0001).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4552287&req=5

f1: The box-and-whisker plot represents the mean and minimum to maximum range of IL-6, IL-8, VEGF and CRP levels in transformed data. Serum levels were measured in 100 control subjects and 90 AMD patients. Among AMD patients 63 had wet type and 27 had dry type AMD. The serum levels of (A) IL-6, (B) IL-8, (C) VEGF and (D) CRP were significantly elevated in AMD patients compared to control subjects (p<0.0001). The levels of (A) IL-6 and (B) IL-8 were significantly elevated in dry AMD patients compared to wet AMD patients. The levels of (C) VEGF and (D) CRP were significantly elevated in wet AMD patients compared to dry AMD patients (p<0.0001).
Mentions: The ANOVA for λ= 0.413 that yielded the lowest error sums of squares was used for hypothesis testing. M-ANOVA showed that serum levels of IL-6, IL-8, VEGF and CRP were significantly elevated in AMD patients (p<0.0001; Wilk’s λ = 0.064; F= 278.7); however, these levels were not found to be associated with gender (p<0.560; Wilk’s λ = 0.997; F= 0.463). The levels of all these factors were found significantly associated with the type of AMD that is wet or dry (p<0.0001; Wilk’s λ = 0.018; F= 147.406). IL-6 and IL-8 levels were significantly increased in patients with dry AMD (p<0.0001), while serum VEGF and CRP levels were significantly elevated in patients with wet AMD (p<0.0001; Figure 1A-D). There was no significant difference in the serum levels of inflammatory factors with respect to age groups (p>0.705; Wilk’s λ = 0.983; F=0.631; Table 3). No significant change was observed in the concentration of IL-6, IL-8, VEGF, and CRP with respect to the pattern of AMD (p<0.302; Wilk’s λ = 0.882; F=1.202; Table 4).

Bottom Line: For rs1800795, patients with the GG genotype showed significantly raised levels of IL-6 compared to those with GC and CC genotypes (p<0.0001).Serum IL-8 levels were significantly higher in patients with the GG genotype compared to the GC and CC genotypes for the single nucleotide polymorphism (SNP) rs2227543 (p<0.002).Similarly, significantly higher VEGF levels were detected for genotype TT for rs3025039 SNP (p<0.038).

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Animal and Human Physiology, Quaid-i-Azam University, Islamabad, Pakistan.

ABSTRACT

Purpose: To study the association of serum levels of inflammatory mediators and angiogenic factors with genetic polymorphism in Pakistani age-related macular degeneration (AMD) patients.

Methods: This was a cross-sectional and case-control study that included 90 AMD patients diagnosed through slit-lamp examination, fundoscopy, and ocular coherence tomography. For reference and comparison purposes, 100 healthy age-matched subjects (controls) were also recruited. IL-6, IL-8, VEGF, and CRP levels were estimated in the serum samples of patients and control subjects. Using restriction fragment length polymorphism, single nucleotide polymorphisms were studied in IL-6 (rs1800795, rs1800796, rs1800797), IL-8 (rs4073, rs2227306, rs2227543), VEGF (rs3025039, rs699947), and CRP genes (rs1205, rs1130864). Since the data were obtained from a sample population, the Box-Cox transformation algorithm was applied to reduce heterogeneity of error. Multivariate analyses of variance (M-ANOVA) were applied on the transformed data to investigate the association of serum levels of IL-6, IL-8, VEGF, and CRP with AMD. Genotype and allele frequencies were compared through χ(2) tests applying Hardy-Weinberg equilibrium. The serum concentrations of IL-6 and IL-8, VEGF, and CRP between homozygotes and heterozygotes were compared through one-way ANOVA. Significance level was p<0.05.

Results: Compared to control subjects, serum IL-6 (p<0.0001), IL-8 (p<0.0001), VEGF (p<0.0001), and CRP (p<0.0001) levels were significantly elevated in the AMD patients. For rs1800795, patients with the GG genotype showed significantly raised levels of IL-6 compared to those with GC and CC genotypes (p<0.0001). Serum IL-8 levels were significantly higher in patients with the GG genotype compared to the GC and CC genotypes for the single nucleotide polymorphism (SNP) rs2227543 (p<0.002). Similarly, significantly higher VEGF levels were detected for genotype TT for rs3025039 SNP (p<0.038). However, no significant alteration in serum CRP levels was detected in hetero- or homozygotes for rs1205 and rs1130864 SNPs.

Conclusions: Serum IL-6, IL-8, and VEGF levels are substantially increased in AMD, and the levels coincide with polymorphism in the respective gene. No such relationship appears to exist with regard to SNPs of CRP.

No MeSH data available.


Related in: MedlinePlus