ABCMdb

PMID: 17923263

Kitjaroentham A, Hananantachai H, Tungtrongchitr A, Pooudong S, Tungtrongchitr R
R219K polymorphism of ATP binding cassette transporter A1 related with low HDL in overweight/obese Thai males.
Arch Med Res. 2007 Nov;38(8):834-8. Epub 2007 Aug 2., [PubMed]

Sentences

No. Mutations Sentence Comment

6 ABCA1 p.Ile883Met ABCA1 p.Arg219Lys The presence of R219K and I883M genetic variant was determined by PCR-RFLP analysis in 112 overweight/obese and 117 control subjects of both sexes. Login to comment 9 ABCA1 p.Arg219Lys Overweight/obese men carrying the mutant allele of R219K had lower level of HDL than the control ( p 5 0.006). Login to comment 11 ABCA1 p.Ile883Met On the contrary, there was no difference in HDL level among genotypes in I883M polymorphism. Login to comment 15 ABCA1 p.Arg219Lys Although the lower level of HDL in overweight/obese men carrying R219K in comparison to the control suggests the possible involvement of this gene with obesity, further investigations are needed to prove the influence of ABCA1 gene polymorphism on HDL level and to determine whether it could be a genetic determinant of obesity. Login to comment 16 ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys Ó 2007 IMSS. Published by Elsevier Inc. Key Words: ABCA1, Overweight/obese, SNP, Polymorphism, R219K. Login to comment 31 ABCA1 p.Ile883Met ABCA1 p.Arg219Lys Some of these ABCA1 polymorphisms such as R219K (10) and I883M (9) are associated with increased HDL levels. Login to comment 32 ABCA1 p.Ile883Met ABCA1 p.Arg219Lys Some of these ABCA1 polymorphisms such as R219K (10) and I883M (9) are associated with increased HDL levels. Login to comment 33 ABCA1 p.Ile883Met ABCA1 p.Arg219Lys Thus, we studied the prevalence of two frequently occurring common variants of the ABCA1 gene, R219K and I883M polymorphisms, and any association between these two polymorphisms and the lipid profiles of Thai overweight/obese subjects. Login to comment 34 ABCA1 p.Ile883Met ABCA1 p.Arg219Lys Thus, we studied the prevalence of two frequently occurring common variants of the ABCA1 gene, R219K and I883M polymorphisms, and any association between these two polymorphisms and the lipid profiles of Thai overweight/obese subjects. Login to comment 50 ABCA1 p.Arg219Lys R219K (G1051A) The forward primer was 50 -GTATTT TTG CAA GGC TAC CAG TTA CAT TTG ACA A-30 and the reverse primer was 50 -GAT TGG CTT CAG GAT GTC CAT GTT GGA A-30 . Login to comment 51 ABCA1 p.Arg219Lys R219K (G1051A) The forward primer was 50 -GTATTT TTG CAA GGC TAC CAG TTA CAT TTG ACA A-30 and the reverse primer was 50 -GAT TGG CTT CAG GAT GTC CAT GTT GGA A-30 . Login to comment 52 ABCA1 p.Ile883Met I883M (A3044G) The forward primer was constructed for EcoRV recognition site (bold), 50 -GAG AAG AGC CAC CCT GGT TCC AAC CAG AAG AGG AT-30 and the reverse primer was 50 -AAG GCA GGA GAC ATC GCT T-30 . Login to comment 53 ABCA1 p.Ile883Met I883M (A3044G) The forward primer was constructed for EcoRV recognition site (bold), 50 -GAG AAG AGC CAC CCT GGT TCC AAC CAG AAG AGG AT-30 and the reverse primer was 50 -AAG GCA GGA GAC ATC GCT T-30 . Login to comment 61 ABCA1 p.Ile883Met ABCA1 p.Arg219Lys Obviously, carrier frequency was high, 60e65% for R219K and almost 90% for I883M. Login to comment 62 ABCA1 p.Ile883Met ABCA1 p.Arg219Lys Obviously, carrier frequency was high, 60e65% for R219K and almost 90% for I883M. Login to comment 63 ABCA1 p.Ile883Met ABCA1 p.Arg219Lys To determine whether the presence of the mutant allele of the two variants (K allele for R219K and M allele for I883M) affects the HDL levels of overweight/obese subjects compared with the control, the HDL levels of the obese and control groups were compared according to their genotype, as shown in Table 3. Login to comment 64 ABCA1 p.Ile883Met ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys To determine whether the presence of the mutant allele of the two variants (K allele for R219K and M allele for I883M) affects the HDL levels of overweight/obese subjects compared with the control, the HDL levels of the obese and control groups were compared according to their genotype, as shown in Table 3. Login to comment 65 ABCA1 p.Arg219Lys A difference was observed in male subjects carrying the mutant allele R219K. Login to comment 66 ABCA1 p.Arg219Lys Bivariate logistic regression was used to test support for the suggestion that the low HDL levels found in overweight/obese men carrying the mutant R219K allele is the result of ABCA1 gene polymorphism. Login to comment 67 ABCA1 p.Ile883Met ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys Bivariate logistic regression was used to test support for the suggestion that the low HDL levels found in overweight/obese men carrying the mutant R219K allele is the result of ABCA1 gene polymorphism. Login to comment 68 ABCA1 p.Ile883Met ABCA1 p.Arg219Lys Table 4 shows the logistic regression and odds ratios for possible association between HDL at cutoff point 35 mg/dL and obesity, cholesterol, triglycerides, LDL, the two ABCA1 polymorphisms-R219K and I883M-and gender. Login to comment 69 ABCA1 p.Arg219Lys Accordingly, most of the overweight and obese men carrying the R219K mutant allele appeared to have HDL !50 mg/dL compared with the control (Figure 1), although they were smaller in number (22 vs. 63). Login to comment 70 ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys Accordingly, most of the overweight and obese men carrying the R219K mutant allele appeared to have HDL !50 mg/dL compared with the control (Figure 1), although they were smaller in number (22 vs. 63). Login to comment 71 ABCA1 p.Arg219Lys Triglyceride was another parameter found to be higher in obese men carrying the R219K mutant allele. Login to comment 72 ABCA1 p.Ile883Met No difference was observed between carriers and noncarriers of the M allele of the I883M polymorphism (data not shown). Login to comment 73 ABCA1 p.Ile883Met No difference was observed between carriers and noncarriers of the M allele of the I883M polymorphism (data not shown). Login to comment 76 ABCA1 p.Ile883Met ABCA1 p.Arg219Lys Our result was 61.61% in overweight/obese and 66.67% for R219K; for I883M, it was 87.5% and 90.18% for overweight/obese and control, respectively. Login to comment 77 ABCA1 p.Ile883Met ABCA1 p.Arg219Lys Our result was 61.61% in overweight/obese and 66.67% for R219K; for I883M, it was 87.5% and 90.18% for overweight/obese and control, respectively. Login to comment 78 ABCA1 p.Arg219Lys However, this agrees with our result because the carrier frequency of R219K in Japanese is 74.6% (12). Login to comment 79 ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys However, this agrees with our result because the carrier frequency of R219K in Japanese is 74.6% (12). Login to comment 80 ABCA1 p.Ile883Met ABCA1 p.Arg219Lys Both polymorphisms appear to be more common among populations of Asian ethnicity than Westerners because R219K carrier frequency in Europeans is 46% (10). Login to comment 81 ABCA1 p.Ile883Met Furthermore, I883M is common in the Japanese as the carrier frequency is 65.4% (12). Login to comment 82 ABCA1 p.Ile883Met I883M SNP has been reported to be associated with variation in HDL level (9,10,12,13). Login to comment 83 ABCA1 p.Ile883Met ABCA1 p.Ile883Met I883M SNP has been reported to be associated with variation in HDL level (9,10,12,13). Login to comment 84 ABCA1 p.Ile883Met Although we did not find an association between I883M and any lipid parameter, new findings from a bioinformatics approach support the suggestion that this is still a functional variant. Login to comment 89 ABCA1 p.Ile883Met ABCA1 p.Ile883Met ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys Frequency of the two ABCA1 SNPs-R219K and I883M-in overweight/obese and control subjects ABCA1 genotype Overweight/obese n (%) Control n (%) Odds ratio (95% CI) p value* R219K n 5 112 n 5 117 219RR 43 39 0.800 0.422 219RK &#fe; KK 57&#fe;12 (61.61%) 65&#fe;13 (66.67%) (0.450e1.430) I883M n 5 112 n 5 112 883II 14 11 0.760 883IM &#fe; MM 47&#fe;51 (87.50%) 57&#fe;44 (90.18%) (0.310e1.890) 0.520 *p value 0.05 or less was considered statistically significant. Login to comment 90 ABCA1 p.Ile883Met ABCA1 p.Ile883Met ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys Frequency of the two ABCA1 SNPs-R219K and I883M-in overweight/obese and control subjects ABCA1 genotype Overweight/obese n (%) Control n (%) Odds ratio (95% CI) p value* R219K n 5 112 n 5 117 219RR 43 39 0.800 0.422 219RK þ KK 57þ12 (61.61%) 65þ13 (66.67%) (0.450e1.430) I883M n 5 112 n 5 112 883II 14 11 0.760 883IM þ MM 47þ51 (87.50%) 57þ44 (90.18%) (0.310e1.890) 0.520 *p value 0.05 or less was considered statistically significant. Login to comment 91 ABCA1 p.Arg219Lys Although several reports have confirmed that the K allele of R219K is associated with a slightly higher HDL concentration (10,15), this is not consistent with our finding in overweight/obese subjects. Login to comment 92 ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys Although several reports have confirmed that the K allele of R219K is associated with a slightly higher HDL concentration (10,15), this is not consistent with our finding in overweight/obese subjects. Login to comment 93 ABCA1 p.Arg219Lys The overweight/obese men carrying R219K had significantly lower HDL concentrations than their controls, although a small number of individuals was tested. Login to comment 100 ABCA1 p.Arg219Lys Lipid profiles of noncarriers and carriers of the K allele of the R219K polymorphism in overweight/obese and control subjects by gender Genotype RR RK &#fe; KK Obese Control p value* Obese Control p value* Men n 5 18 n 5 33 n 5 22 n 5 63 Cholesterol 211.00 203.00 0.937 220.50 202.00 0.177 (103.00e374.00) (127.00e284.00) (136.00e276.00) (129.00e279.00) HDL 50.50 44.00 0.206 45.00 50.00 0.006* (31.00e64.00) (28.00e64.00) (33.00e69.00) (33.00e86.00) LDL 133.90 138.20 0.460 129.00 117.40 0.748 (26.00e291.00) (55.00e210.00) (75.00e193.00) (50.00e205.00) Triglycerides 137.50 138.00 0.261 188.50 118.00 0.000 (62.00e269.00) (47.00e269.00) (71.00e342.00) (35.00e327.00) Women n 5 25 n 5 6 n 5 47 n 5 15 Cholesterol 211.00 182.00 0.937 223.00 212.00 0.406 (139.00e427.00) (159.00e352.00) (136.00e388.00) (167.00e319.00) HDL 51.00 59.50 0.423 50.00 43.00 0.097 (29.00e78.00) (27.00e71.00) (34.00e79.00) (31.00e61.00) LDL 138.80 119.60 0.726 145.00 139.00 0.824 (44.00e359.00) (85.00e259.00) (50.00e284.00) (107.00e236.00) Triglycerides 133.00 110.50 0.516 117.00 88.00 0.565 (48.00e351.00) (45.00e307.00) (48.00e397.00) (50.00e355.00) *Mann-Whitney U Test (two-tailed). Login to comment 101 ABCA1 p.Arg219Lys Lipid profiles of noncarriers and carriers of the K allele of the R219K polymorphism in overweight/obese and control subjects by gender Genotype RR RK þ KK Obese Control p value* Obese Control p value* Men n 5 18 n 5 33 n 5 22 n 5 63 Cholesterol 211.00 203.00 0.937 220.50 202.00 0.177 (103.00e374.00) (127.00e284.00) (136.00e276.00) (129.00e279.00) HDL 50.50 44.00 0.206 45.00 50.00 0.006* (31.00e64.00) (28.00e64.00) (33.00e69.00) (33.00e86.00) LDL 133.90 138.20 0.460 129.00 117.40 0.748 (26.00e291.00) (55.00e210.00) (75.00e193.00) (50.00e205.00) Triglycerides 137.50 138.00 0.261 188.50 118.00 0.000 (62.00e269.00) (47.00e269.00) (71.00e342.00) (35.00e327.00) Women n 5 25 n 5 6 n 5 47 n 5 15 Cholesterol 211.00 182.00 0.937 223.00 212.00 0.406 (139.00e427.00) (159.00e352.00) (136.00e388.00) (167.00e319.00) HDL 51.00 59.50 0.423 50.00 43.00 0.097 (29.00e78.00) (27.00e71.00) (34.00e79.00) (31.00e61.00) LDL 138.80 119.60 0.726 145.00 139.00 0.824 (44.00e359.00) (85.00e259.00) (50.00e284.00) (107.00e236.00) Triglycerides 133.00 110.50 0.516 117.00 88.00 0.565 (48.00e351.00) (45.00e307.00) (48.00e397.00) (50.00e355.00) *Mann-Whitney U Test (two-tailed). Login to comment 103 ABCA1 p.Ile883Met ABCA1 p.Ile883Met ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys Logistic regression results for relationship between HDL at cutoff point 35 mg/dL and obesity, cholesterol, triglycerides, LDL, ABCA1 polymorphisms at R219K and I883M, and gender Variables Odds ratio 95% CI p value* Obesity 0.365 0.027e4.971 0.449 Cholesterol 2.775 1.502e5.129 0.001 Triglycerides 0.817 0.724e0.920 0.001 LDL 0.358 0.192e0.665 0.001 R219K 0.824 0.089e7.622 0.864 I883M 0.634 0.027e14.942 0.777 Gender 1.816 0.173e19.111 0.619 *p value 0.05 or less was considered statistically significant. Login to comment 104 ABCA1 p.Ile883Met ABCA1 p.Ile883Met ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys Logistic regression results for relationship between HDL at cutoff point 35 mg/dL and obesity, cholesterol, triglycerides, LDL, ABCA1 polymorphisms at R219K and I883M, and gender Variables Odds ratio 95% CI p value* Obesity 0.365 0.027e4.971 0.449 Cholesterol 2.775 1.502e5.129 0.001 Triglycerides 0.817 0.724e0.920 0.001 LDL 0.358 0.192e0.665 0.001 R219K 0.824 0.089e7.622 0.864 I883M 0.634 0.027e14.942 0.777 Gender 1.816 0.173e19.111 0.619 *p value 0.05 or less was considered statistically significant. Login to comment 109 ABCA1 p.Ser1731Cys Recently, a reported bioinformatics approach to predict and experimentally test the functional consequence of ABCA1 genetic variation found that the HEK293 cell transfected with S1731C cSNP allele expressed low-level ABCA1 protein and reduced cholesterol efflux. Login to comment 110 ABCA1 p.Ser1731Cys Recently, a reported bioinformatics approach to predict and experimentally test the functional consequence of ABCA1 genetic variation found that the HEK293 cell transfected with S1731C cSNP allele expressed low-level ABCA1 protein and reduced cholesterol efflux. Login to comment 111 ABCA1 p.Arg219Lys In conclusion, our study showed that the R219K variant allele was associated with low levels of HDL in Thai overweight/obese men compared with their controls. Login to comment 112 ABCA1 p.Ile883Met ABCA1 p.Arg219Lys In conclusion, our study showed that the R219K variant allele was associated with low levels of HDL in Thai overweight/obese men compared with their controls. Login to comment 113 ABCA1 p.Ile883Met However, I883M showed no association with any lipid profile parameters and both polymorphisms appear to be common variants among Thai and other Asian countries. Login to comment