
ASSOCIATION OF THE APOLIPOPROTEIN A-I GENE POLYMORPHISMS WITH CARDIOVASCULAR DISEASE RISK FACTORS AND ATHEROGENIC INDICES IN PATIENTS FROM ASSAM, NORTHEAST INDIA
Bora K1,2,*, Pathak MS2, Borah P3, Hussain Md.I.3, Das D4
*Corresponding Author: : Dr. Kaustubh Bora, Regional Medical Research Centre, Northeast Region, Indian Council of Medical Research (ICMR), P.O. Box 105, Dibrugarh-786001, Assam, India. Tel: +91-943-557-2062. Fax: +91-364-253-8003. E-mail: kaustubhbora1@gmail.com
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RESULTS
The baseline characteristics of the study subjects are presented in Table 1. The individuals in the case and the control groups were comparable (p >0.05) in terms of age and sex composition, and smoking and alcohol use status. Concentration of HDL-C was significantly lower in the case group than in the control group, as expected. Furthermore, the case group individuals had significantly higher (p <0.05) measures of obesity (BMI and WC), systolic and diastolic BP, lipid profile parameters (TC, TG, LDL-C and VLDL-C) and atherogenic indices in comparison to the control group individuals. None of the subjects in the study were vegetarians. During genotyping, we detected GG, GA and AA genotypes for the G-75A site, and CC and CT genotypes for the C+83T site (Figure 1). Distribution of G-75A and C+83T Single Nucleotide Polymorphisms. The genotype, allelic and diplotype frequencies for G-75A and C+83T polymorphic loci are summarized in Table 2. Both the polymorphisms were in Hardy-Weinberg equilibrium. For the G-75A site, the GG
genotype was most common, followed by GA and AA. The frequencies of GG, GA and AA genotypes were comparable between the case and the control groups (χ2 = 1.692, df = 2, p = 0.43). The allelic frequencies in the two groups were also comparable (minor A allele frequency = 0.205 in cases and 0.235 in controls, χ2 = 0.364, df = 1, p = 0.55). For the C+83T site, the homozygous TT genotype was not detected in either the cases or the controls. However, the frequency of CC and CT genotypes were comparable in the two groups (χ2 = 0.047, df = 1, p = 0.83). Similarly, the minor T allele frequency (0.055 in cases and 0.065 in controls) was also comparable (χ2 = 0.044, df = 1, p = 0.83). Five diplotypes were detected for the two polymorphic sites (Table 2). The diplotype frequencies did not vary significantly between the case and the control groups (χ2 = 2.041, df = 4, p = 0.73). Association of G-75A and C+83T Single Nucleotide Polymorphisms with Decreased High Density Lipoprotein Cholesterol. Neither the genotypic variants nor the allelic variants of the G-75A or the C+83T polymorphism detected in the study were associated with HDL-C status (Table 3). Association of G-75A and C+83T Single Nucleotide Polymorphisms with Other Lipid Fractions. The G-75A SNP was associated with LDL-C levels (Table 4). Values of LDL-C were significantly (p <0.05) higher in the A allele-containing controls as compared to the GG homozygotes. No significant association (p >0.05)
was observed with other components of lipid profile. The C+83T locus was associated with TG and VLDL-C levels (Table 5). The case subjects with the CC genotype had significantly (p <0.05) higher TG and VLDL-C values than their CT counterparts. These findings persisted in the overall sample. Association of G-75A and C+83T Single Nucleotide Polymorphisms with Atherogenic Indices. The G-75A polymorphism was associated with several atherogenic indices (Table 4). The AA homozygotes had significantly (p <0.05) elevated non-HDL-C and CRI-II values, whereas the G allele carriers had significantly (p <0.05) diminished CRI-I and AC values. On the other hand, the C+83T polymorphism was associated with the AIP values (Table 5). The CC subjects had significantly (p <0.05) raised AIP than their CT counterparts. Association of G-75A and C+83T Single Nucleotide Polymorphisms with Obesity Indices and Blood Pressure. The G-75A and C+83T loci were not associated with obesity and BP in the subjects under the present study. Values of WC, BMI and systolic and diastolic BP were comparable (p >0.05) across the different genotypes detected for the two polymorphic sites (Tables 4 and 5).
Association of Diplotypes with the Cardiovascular Disease Risk Factors. The CVD risk factors did not differ significantly across the five diplotypes obtained in the current study (data not shown). Effect Size and Power. The G-75A locus produced medium-to-large sized effects (0.25 < Cohen’s f <0.4) on the CVD risk factors (non-HDL-C, CRI-I, CRI-II, AC and LDL-C values) with which it was associated, while the effect size of the C+83T locus on CVD risk factors (TG, VLDL-C and AIP) was small-to-medium (0.1
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