Analysis of polymorphism of the interleukin-6 gene in Thai subjects with osteoporosis.

Osteoporosis is the imbalance between bone formation by osteoblast and bone resorption by osteoclast. The genetic factors play an important role in determining bone mass and several genes probably act as regulators of this process. Interkeukin-6 (IL-6) is one of the candidate genes to regulate bone density, since IL-6 has some effect on stimulation of osteoclast resorption and has been implicated in the pathogenesis of bone loss associated with estrogen deficiency. We investigated the relationship between bone mineral density (BMD) and a polymorphic AT rich repeat in the 3' flank of the IL-6 gene in 272 Thai subjects. The subjects were classified into 3 groups i.e. normal healthy control (n=95), border-line (n=112) and osteoporotic patients (n=65). Five alleles different in sizes were identified (designated a, b, c, e and f). It was observed that c/c was the most common genotype in Thais (86.76%). The other genotype frequencies were 0.74, 3.31, 8.09, 0.74 and 0.37 for a/c, b/c, c/e, c/f and b/e genotypes, respectively. The common genotype was different from the Caucasians in a previous study. These frequencies were significantly different from the Caucasians (p<0.05). There was no significant relationship between 3' flanking AT repeat of the IL-6 genotypes and the BMD values of the distal forearm that were determined by One-way ANOVA (p>0.05). Additionally, the impact of the IL-6 genotypes on risk of osteoporosis was assessed by determination of the odds ratio. The c/e genotype may be a protective factor of osteoporosis. On the contrary, the b/c and c/c genotypes were considered to be risk factors of osteoporosis.

Screening for a D9N common mutation in exon 2 of the LPL gene in Thai normolipidemic and hyperlipidemic subjects.

Lipoprotein lipase (LPL) is a multifunctional protein, playing a major role in the hydrolysis of triglyceride-rich lipoproteins. It also affects the maturation of high density lipoprotein (HDL) and low density lipoprotein (LDL). A D9N substitution is a frequent mutation found in exon 2 of the LPL gene. It is due to a G --> A transition causing a substitution of Asp by Asn at amino acid residue 9 of the protein. This mutation was screened for in 94 Thai primary dyslipidemic (46 hypercholesterolemic and 48 combined hyperlipidemic) subjects compared to 32 normal healthy subjects using PCR-RFLP. Such a mutation has not, yet, been detected in any of these Thai subjects.

Polymorphism of the gene encoding lipoprotein lipase in thai primary hyperlipoproteinemias.

Lipoprotein lipase (LPL) plays a central role in the clearance of very low density lipoprotein (VLDL) and chylomicrons from the circulation. It also affects the maturation of high density lipoprotein (HDL) and low density lipoprotein (LDL). LPL is an important candidate gene in determining the risk factor in metabolic disorders including primary hyperlipidemia. Our study is the first report from Thailand on the characterization of two common DNA polymorphisms, i.e Pvu II and Hind III at introns 6 and 8, respectively of the LPL gene in 94 Thai dyslipidemic subjects compared to 32 normolipidemic subjects using PCR-RFLP. It was observed that the frequencies of the cut and uncut alleles of Pvu II were 0.67 and 0.33 in normolipidemic subjects. Such frequencies were 0.64 and 0.36 in hyperlipidemic subjects. Additionally, the frequencies of the cut and uncut alleles of Hind III were found to be 0.73 and 0.27 in normolipidemic subjects. They were 0.85 and 0.15 in hyperlipidemic subjects. The allele frequencies of the Hind III but not Pvu II polymorphism in hyperlipidemic subjects were significantly different from normolipidemic subjects (p<0.05). The relation between these polymorphisms and lipid traits was not statistically significant (p>0.05).