Five of the gallstone associations are protein-altering variants, and three (HNF4A p.Thr139Ile, SERPINA1 p.Glu366Lys, and SLC10A2 p.Pro290Ser) conferred per-allele odds ratios for gallstone disease of 1.30-1.36.
Five of the gallstone associations are protein-altering variants, and three (HNF4A p.Thr139Ile, SERPINA1 p.Glu366Lys, and SLC10A2 p.Pro290Ser) conferred per-allele odds ratios for gallstone disease of 1.30-1.36.
Mutational analysis of ABCB4, screening for copy number variations by multiplex ligation-dependent probe amplification, genotyping for low expression allele c.1331T>C of ABCB11 and genotyping for variation c.55G>C in ABCG8 previously associated with cholesterol gallstones in adults was performed in 35 pediatric subjects with idiopathic gallstones who fulfilled the clinical criteria for low phospholipid-associated cholelithiasis syndrome (LPAC, OMIM #600803) and in 5 young females with suspected LPAC and their families (5 probands, 15 additional family members).
A known mutation, c.490C＞T (p. Arg164(＊)), in exon 4 and a novel mutation, c.1949T＞G (p.Leu650Arg), in exon 13 of ABCG8 were detected in the proband and her sister, who had elevated sterols but low LDL-C levels and no xanthomas.
ABCG5 rs6756629 is in strong linkage disequilibrium with rs11887534 (D19H), a variant previously associated with gallstone disease risk in populations of European-descent.
Carriers of the CG genotype of ABCG8 rs11887534 had higher risk of biliary stones [odds ratio (OR) = 2.3, 95% confidence interval (CI) 0.82-6.5), gallbladder cancer (OR = 4.3, 95% CI 1.7-10.4) and bile duct cancer (OR = 1.94, 95% CI 0.64-5.91), compared with carriers of the GG genotype.
Carriers of the CG genotype of ABCG8 rs11887534 had higher risk of biliary stones [odds ratio (OR) = 2.3, 95% confidence interval (CI) 0.82-6.5), gallbladder cancer (OR = 4.3, 95% CI 1.7-10.4) and bile duct cancer (OR = 1.94, 95% CI 0.64-5.91), compared with carriers of the GG genotype.
Carriers of the ABCG8 haplotype C-C (rs4148217-rs11887534) had a 4.16-fold (95% CI 1.71-10.1) risk of gallbladder cancer compared with those carrying the C-G haplotype.
In our study we investigated the contribution of heterozygosity for common variations considered either potentially pathogenic or susceptibility alleles for cholesterol cholelithiasis in adults (c.523A>G (p.Thr175Ala) and c.1954A>G (p.Arg652Gly) in ABCB4, c.1331T>C (p.Val444Ala) in ABCB11 and c.55 G>C (p.Asp19His) in ABCG8) to the aetiology of paediatric idiopathic gallstone disease.
In our study we investigated the contribution of heterozygosity for common variations considered either potentially pathogenic or susceptibility alleles for cholesterol cholelithiasis in adults (c.523A>G (p.Thr175Ala) and c.1954A>G (p.Arg652Gly) in ABCB4, c.1331T>C (p.Val444Ala) in ABCB11 and c.55 G>C (p.Asp19His) in ABCG8) to the aetiology of paediatric idiopathic gallstone disease.
In our study we investigated the contribution of heterozygosity for common variations considered either potentially pathogenic or susceptibility alleles for cholesterol cholelithiasis in adults (c.523A>G (p.Thr175Ala) and c.1954A>G (p.Arg652Gly) in ABCB4, c.1331T>C (p.Val444Ala) in ABCB11 and c.55 G>C (p.Asp19His) in ABCG8) to the aetiology of paediatric idiopathic gallstone disease.
In our study we investigated the contribution of heterozygosity for common variations considered either potentially pathogenic or susceptibility alleles for cholesterol cholelithiasis in adults (c.523A>G (p.Thr175Ala) and c.1954A>G (p.Arg652Gly) in ABCB4, c.1331T>C (p.Val444Ala) in ABCB11 and c.55 G>C (p.Asp19His) in ABCG8) to the aetiology of paediatric idiopathic gallstone disease.
Alleles of ABCG8 and ABO associated with elevated phytosterol levels displayed significant associations with increased CAD risk (rs4245791 odds ratio, 1.10; 95% CI, 1.06 to 1.14; P=2.2 x 10(-6); rs657152 odds ratio, 1.13; 95% CI, 1.07 to 1.19; P=9.4 x 10(-6)), whereas alleles at ABCG8 associated with reduced phytosterol levels were associated with reduced CAD risk (rs41360247 odds ratio, 0.84; 95% CI, 0.78 to 0.91; P=1.3 x 10(-5)).
Studies have identified single nucleotide polymorphisms (SNP) D19H and T400K in the cholesterol transporter gene ATP-binding cassette, subfamily G, member 8 (ABCG8) in patients with cholesterol gallstones.
Alleles of ABCG8 and ABO associated with elevated phytosterol levels displayed significant associations with increased CAD risk (rs4245791 odds ratio, 1.10; 95% CI, 1.06 to 1.14; P=2.2 x 10(-6); rs657152 odds ratio, 1.13; 95% CI, 1.07 to 1.19; P=9.4 x 10(-6)), whereas alleles at ABCG8 associated with reduced phytosterol levels were associated with reduced CAD risk (rs41360247 odds ratio, 0.84; 95% CI, 0.78 to 0.91; P=1.3 x 10(-5)).
Determinations of allele frequencies of four common ABCG8 polymorphisms (D19H, Y54C, T400K, and A632V) were carried out in 241 unrelated patients with ischemic stroke, 148 patients with coronary heart disease, and 191 blood donors (controls).