ADIPOCYTE “FATTY ACID BINDING PROTEIN” GENE POLYMORPHISMS (rs1054135, rs16909196 AND rs16909187) IN JORDANIANS WITH OBESITY AND TYPE 2 DIABETES MELLITUS
El-Ryalat S.W.1, Irshaid Y.M.1*, Abujbara M.2, El-Khateeb M.2, Ajlouni K.M.2
*Corresponding Author: Prof. Yacoub M. Irshaid MD, PhD, Department of Pharmacology, College of Medicine, The University of Jordan, Amman 11942, Jordan. Phone No.: +962 777818284, Fax No.: +962 6 5300820, Email Addresses: y.irshaid@ju.edu.jo
page: 63

RESULTS

The study was performed on 397 subjects who were divided into 4 groups. Males were more than females (252 subjects, 63.5%). The age range was 18-80 years. The number of subjects in each group, the demographics, and clinical laboratory findings of subjects enrolled in the study are presented in (Table 1). The control group (group 4) has the lowest values for triglycerides, total cholesterol, LDL-cholesterol, hemoglobin A1C and body mass index. HDL-cholesterol was lowest in group 3 (Non-diabetic but overweight or obese). Concerning age, group 4 subjects were the youngest. The genotype and allele frequencies of the three SNPs (rs1054135, rs16909196 and rs16909187) in the whole sample studied are presented in (Table 2). The minor allele frequencies were 0.068, 0.202, and 0.199 for rs1054135, rs16909196 and rs16909187, respectively. The Hardy-Weinberg equilibrium was calculated in all the studied subjects together and in the control group alone for each of the 3 SNPs. The results showed that the 3 SNPs followed the Hardy-Weinberg equilibrium in the control group who were non-obese and non-diabetic, and that equilibrium was not affected by the disease states. The results are presented in (Table 3). The distribution of the genotypes of the 3 SNPs among the 4 groups studied is presented in (Table 4). The genotype distribution was similar for the 3 SNPs in group 1 (Obese or overweight diabetics) compared to group 4 (normal weight non-diabetics) and in group 2 (diabetics with normal weight) compared to group 4. The distribution of rs1054135 genotypes were also similar in group 3 (Non-diabetic but overweight or obese) compared to group 4. The distribution of the genotypes of rs16909196 and rs16909187 was similar in group 2 compared to group 4. However, the distribution of the genotypes in group 3 was significantly different from that in group 4. Regarding rs16909196, the homozygous wild type genotype (AA), was significantly higher in group 3 than in group 4 (OD = 2.26, 95% CI 1.24-4.14, z score 2.649 and p-value 0.01). There was no difference in the homozygous minor allele genotype (TT) between the two groups (OD = 0.29, 95% CI 0.06-1.49, z score 1.479 and p-value 0.14). The heterozygous genotype (AT) was higher in the control group (OD = 0.52, 95% CI 0.28-0.96, z score 2.08 and p-value 0.04). This result may indicate that the wild type homozygous genotype AA of rs16909196 SNP may be a risk factor for obesity, while the heterozygous AT may be protective. With regard to rs16909187, the homozygous wild type genotype CC was significantly higher in group 3 than in group 4 (OD = 2.17, 95% confidence interval 1.18-3.96, z score 2.505 and p-value 0.01). There was no difference in the homozygous minor allele genotype (TT) between the two groups (OD = 0.29, 95% CI 0.06-1.49, z score 1.479 and p-value 0.14). Concerning the heterozygous genotype (CT), it was higher in the control group (OD = 0.54, 95% CI 0.29-1.01, z score 1.926 and p-value 0.05), but it did not each statistical significance. This result may indicate that the wild type homozygous genotype CC of rs16909187 SNP may be a risk factor for obesity, while the heterozygous may be protective. The association between (rs1054135, rs16909196 and rs16909187) haplotypes and obesity is presented in (Table 5). The haplotype of the wild type allele of the 3 SNPs (GAC) is significantly associated with obesity or overweight (p-value = 0.02). A higher proportion of the obese or overweight subjects had this haplotype than control group. While the haplotype composed of the wild type allele of rs1054135 and the recessive alleles of rs16909196 and rs16909187 (GTT) was found at higher proportion in the control group when compared to the obese or overweight group, but the difference did not reach statistical significance (p = 0.05). The haplotypes AAC was not significantly associated with obesity and overweight and diabetes (p = 0.33). The linkage disequilibrium (LD) analysis, estimation of haplotype diversity among the four groups was performed using Haploview 4.2 population genetic analysis software (Table 6). The D′ and r2 values obtained were used to assess linkage disequilibrium. The results show that rs16909196, and rs16909187 SNPs have a strong linkage disequilibrium in the control group (D′ = 1, r2=0.97). These 2 SNPs remained in strong linkage disequilibrium in the other 3 groups as well. The SNP rs1054135 was not in linkage disequilibrium with either rs16909187 (D′ = 1, r2=0.03) or rs16909196 (D′ = 1, r2=0.03) SNPs. Concerning the association of FABP4 gene polymorphisms (rs1054135, rs16909196 and rs16909187) with serum concentrations of LDL, HDL, TC and TG among the studied groups, only the rs1054135 SNP showed significant association with higher LDL levels in the third group subjects who are overweight or obese (p- value=0.03). However, there was no significant association between rs1054135 SNP and HDL, TC and TG levels. The rest of the results in this regard are not presented.



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