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Association of Glutathione-S-Transferase P1 (GSTP1) and Group-Specific Component (GC) Polymorphism with the Risk of Asthma in Pakistani Population.

Byline: Najiya Al-Arifa and Nusrat Jahan

ABSTRACT

Risk of asthma is associated with complex interplay of genetic, ethnic and environmental factors therefore asthma prevalence in various ethnic groups cannot be predicted from the interethnic genotype and allelic frequencies. Currently there is very limited data available regarding the association of genetic polymorphisms with asthma in Pakistani population. The following study was aimed to assess the association of glutathione-S-transferase P1 (GSTP1) and group-specific component (GC) with asthma in adult Pakistani population. Genetically unrelated and clinically diagnosed 200 asthmatics along with 200 healthy controls were voluntarily recruited for this study. Genotyping was performed using conventional PCR. GSTP1 and GC polymorphisms were determined by using restriction fragment length polymorphism (RFLP) technique.

The homozygous GSTP1 Ile/Ile genotype was found to be significantly associated (p = 0.003) with the risk of asthma whereas the homozygous GSTP1 Val/Val genotype (p = 0.19) was found to be more frequent in control population than in the patients (6% and 10%, respectively). The GC polymorphism GC2 homozygote was also significantly associated with the risk of asthma (p = 0.05). Genotype frequencies of the studied GSTP1 and GC polymorphisms in both asthmatics and controls are provided in Table IV.

A significant association between asthma and the homozygous GSTP1 Ile/Ile genotype (OR = 2.27; 95% CI, 1.339 - 3.854; p = 0.003) was observed in the studied population whereas the homozygous GSTP1 Val/Val genotype (OR = 0.57; 95% CI, 0.273 - 1.209; p = 0.19) was more frequently observed in the controls than the cases (6% and 10% respectively). This higher frequency of the Val variable is an indicator of its possible protective role against asthma. As for the GC polymorphisms, the GC2 homozygote (GC2/GC2) was found to be significantly associated with asthma (OR = 3.14; 95% CI, 1.786 - 5.535; p = <0.001), whereas the GC1S homozygote (GC1S/GC1S) (OR = 0.52; 95% CI, 0.203 - 1.335; p = 0.250) was observed less frequently in asthmatics and more in the control group (3.5% and 6.5%, respectively). The higher rate of GCIS in control population may be an indicator of the protective role of GC1S variant against the susceptibility to asthma.

DISCUSSION

This case-control study was performed to assess the association of the GSTP1 and GC polymorphisms with asthma susceptibility in Pakistani population. Our results demonstrate the association of both GSTP1 and GC variants with an increased risk of asthma in Pakistani population as evident from the significant differences in the genotype frequencies of asthmatics and controls.

In present study the asthmatics have exhibited a higher frequency of GSTP1 Ile (A) variant and a lower frequency of GSTP1 Val (G) variant as compared to the control population. These results implicate the homozygous Ile/Ile (AA) with susceptibility to the risk of asthma and suggest a protective role of the homozygous Val/Val (GG) allele against asthma. Several studies concur with our results and have reported similar protective role of the GSTP1 Val/Val genotype and its association with lower risk of asthma than the GSTP1 Ile/Ile (AA) genotype (Spiteri et al., 2000; Hemmingsen et al., 2001; Aynacioglu et al., 2004; Miller et al., 2004). Fryer et al. (2000) studied a population of Northern European white and concluded a 4-10 fold lower risk of asthma for GSTP1 Val/Val homozygotes which corresponds to our own findings. Lee et al. (2004) demonstrated a significantly increased risk of asthma in Ile homozygotes (OR = 5.52; 95% CI, 1.64-21.25) as compared to Val carriers in a Taiwanese cohort.

Asthmatics from South-East Anatolia, Turkey have also exhibited significantly lower GSTP1 Val allele frequency than in control group (3.8% and 12.1% respectively, p = 0.01) (Aynacioglu et al., 2004). Similar observations were concluded by Spiteri et al. (2000) where the frequency of GSTP1 Val/Val genotype was found to be higher in non-atopic asthmatics rather than in atopic asthmatics, furthermore a significant increase in GSTP1 Ile/Ile genotype frequency was observed with increased asthma severity and a parallel decreased in frequency of GSTP1 Val/Val genotype. GSTP1 Ile/Ile frequency was found to increase in patients with established asthma whereas GSTP1 (Val105-Ala114) and GSTP1 (Val105-Val114) confer protective effects in Northern Europeans (Kabesch et al., 2004).

Occurrence of the GSTP1 Val/Val homozygote was found to be more frequent in the control group than the asthmatics in a study carried out on Tunisian Children, moreover there was a higher prevalence of GSTP1 Ile allele in the asthmatic children than the control group (43.8% and 33.5%, respectively; p = 0.002) (Hanene et al., 2007).

Table IV.- Genotype frequencies for the studied polymorphisms.

###Asthma###Control

Gene###SNP###Genotypes###x2###OR###95% CI###p

###n = 200###n = 200

###n (%)###n (%)

GSTP1###rs1695###AA(Ile/Ile)###49(24.5)###25(12.5)###8.77###2.27###1.339 - 3.854###0.003*

###AG(Ile/Val)###51(25.5)###48(24)###0.05###1.084###0.688 - 1.707###0.817

###GG(Val/Val)###12(6)###20(10)###1.66###0.57###0.273 - 1.209###0.19

###A(Ile)###149(74.5)###118(59)###4.45###1.54###1.050 - 2.285###0.035*

###G(Val)###75(37.5)###92(46)

GC###rs4588###GC1F/GC1F###45(22.5)###34(17)###1.61###1.42###0.865 - 2.359###0.204

###GC1S/GC1S###7(3.5)###13(6.5)###1.32###0.52###0.203 - 1.335###0.250

###GC1F/GC1S###18(9)###12(6)###0.90###0.64###0.301 - 1.377###0.341

###rs7041###GC1F/GC2###33(16.5)###23(11.5)###1.70###1.53###0.859 - 2.724###0.191

###GC1S/GC2###31(15.5)###22(11)###1.41###0.67###0.372 - 1.208###0.235

###GC2/GC2###51(25.5)###20(10)###15.70###3.14###1.786 - 5.535### T and asthma, a systematic review and metaanalysis. BMC med. Genet., 12: 93.
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Publication:Pakistan Journal of Zoology
Article Type:Report
Geographic Code:9PAKI
Date:Aug 31, 2016
Words:1070
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