The -514C/T Polymorphism of Hepatic Lipase Gene among Iranian Patients with Coronary Heart Disease.

BACKGROUND: The T allele of the hepatic lipase (HL) C-514T polymorphism was previously found to be associated with lower plasma HL activity. Here, we examined the association between this polymorphism and plasma HDL-cholesterol concentrations in patients with coronary arteries stenosis. METHODS: We studied 342 subjects undergoing coronary angiography in two groups of non CAD (n=146) and CAD (n=196). -514C→T polymorphism was determined using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). RESULTS: After adjustment for age, smoking and body mass index, HDL-cholesterol concentrations were significantly higher in men with the C/T&T/T genotype than those with the C/C genotype(mean 38.6 and 34.7 respectively P=0.01). The frequency of T allele in non CAD was 0.136 and 0.226 in female and male respectively and 0.170 and 0.223 for female and male in CAD subjects. There was no difference in T allele frequency in CAD and none CAD groups in male and female (P=0.466 and 0.722 respectively). CONCLUSION: -514C→T of LIPC gene have a positive effect on HDL-C concentration especially in male gender. However, no difference was determined in frequency of T allele between CAD and normal arteries subjects.

Molecular characterization of Iranian patients with possible familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is an autosomal dominant disorder of lipoprotein metabolism caused mainly by mutations in the low-density lipoprotein receptor (LDLR) and apolipoprotein B 100 (APOB) genes. Until now, the molecular basis of FH has been demonstrated in detail in many populations, but there is still very limited Molecular data concerning FH in Iran. The aim of this study was to characterize the LDLR and APOB gene mutations in an Iranian population. A total of 30 non-related Iranian possible FH subjects were studied. Diagnosis of FH was based on the Dutch Lipid Clinic Network diagnostic criteria. All samples were initially tested for three common APOB gene mutations including R3500Q, R3500 W and R3531C using PCR-RFLP assay. Subsequently, promoter and coding region of the LDLR gene was screened by PCR-SSCP analysis and positive results were confirmed by DNA sequencing. Four previously reported polymorphisms 1413G > A, 1725C > T, 1773T > C and 2140 + 5G > A were found in ~17% (5/30) of population studied. Moreover, no variation was found in APOB gene. Our data indicated that LDLR and APOB gene mutations have not contribution to possible FH in Iranian population studied here. However, we examined three common APOB mutations and LDLR in only 30 patients, and to determine the role of these genes in developing FH in Iran, more FH samples and populations needed to be investigated for the mutations of the related genes.

Genetic Linkage Analysis of 15 DFNB Loci in a Group of Iranian Families with Autosomal Recessive Hearing Loss.

BACKGROUND: Hearing loss (HL) is the most frequent sensory birth defect in humans. Autosomal recessive non-syndromic HL (ARNSHL) is the most common type of hereditary HL. It is extremely heterogeneous and over 70 loci (known as DFNB) have been identified. This study was launched to determine the relative contribution of more frequent loci in a cohort of ARNSHL families. METHODS: Thirty-seven Iranian families including 36 ARNSHL families and 1 family with Pendred syndrome each with ≥ 4 affected individuals, from seven provinces of Iran, were ascertained. DFNB1 contribution was initially studied by DNA sequencing of GJB2 and linkage analysis using the relative STR markers. The excluded families were then subjected to homozygosity mapping for fifteen ARNSHL loci. RESULTS: Sixteen families were found to be linked to seven different known loci, including DFNB1 (6 families), DFNB4 (3 families +1 family with Pendred syndrome), DFNB63 (2 families), DFNB2 (1 family), DFNB7/11 (1 family), DFNB9 (1 family) and DFNB21 (1 family). DNA sequencing of the corresponding genes is in progress to identify the pathogenic mutations. CONCLUSION: The genetic causes were clarified in 43.2% of the studied families, giving an overview of the causes of ARNSHL in Iran. DFNB4 is ranked second after DFNB1 in the studied cohort. More genetic and epigenetic investigations will have to be done to reveal the causes in the remaining families.