الملخص الإنجليزي
Lactose Intolerance (LI) is a common phenomenon associated with unpleasant abdominal symptoms after ingesting lactose containing food. LI is uncommon in milkconsuming societies (Pastoralists and Bedouins). It is a result of lactase deficiency, (hypolactasia). It is classified into three main types: congenital, secondary, and adult type hypolactasia (ATH). This study is concerned mainly with ATH. ATH is an autosomal recessive normal physiological condition, in which the lactase deficiency is a result of the down regulation of the lactase enzyme gene after weaning in mammals including humans. In some ethnic groups, lactase continues to be at high or normal level even after weaning period, a condition known as lactase persistence (LP), allowing them to use dairy products. All methods used for diagnosing LI are based mainly on the activity of lactase in intestine. The most acceptable non-invasive method is the hydrogen breath test (HBT). Hydrogen is measured before and after ingesting lactose which reflects, indirectly, the level of lactase. Since 2002, some single nucleotide polymorphisms (SNPs) have been proposed to be the causative agents of lactase persistence in adults. These variants occur in chromosome 2 in the MCM6 gene adjacent to the lactase gene. T/G-13915 in addition to C/T-13910 are the two SNPs that can explain ATH in Arab countries (C/C-13910 & T/T-13915 genotypes - lactase nonpersistence; T/C or T/T-13910 & G/T or GG-13915 genotypes - lactase persistence). Prevalence of ATH is known to vary among different ethnic populations even in the same country. This study was carried out to explore and investigate SNPs associated with LI and to estimate the prevalence of lactose intolerance among adults in the Sultanate of Oman. A correlation study was carried between phenotype and genotype of LP, via lactose hydrogen breath test (LHBT), of 62 healthy adult Omanis and genotype of different SNPs associated with LI. Out of the 62 subjects, three (5%) were non hydrogen producers; 49 (79%) were lactose malabsorbers and 10 (16%) were lactose absorbers. Phenotype-genotype correlation was based on 50 subjects with complete data. All FortyOne individuals with C/C-13910 and T/T-13915 genotypes had positive breath tests (20 ppm); eight of nine individuals with C/T-13910 or T/G-13915 genotypes had negative breath tests (<20 ppm). The agreement between phenotype and genotype using Kappa value was at 0.93. In a second population based study, 563 Omani individuals were genotyped using direct sequencing and restriction fragment length polymorphism (RFLP). The genotype analysis revealed that the frequency of LI is ranging from 80% in the North of Oman declining to 20% in the South. The G-13915 allele was found to be associated strongly with LP and limited to Arab groups while T-13910 allele is specific, but not limited, to Omanis of Asian origin. The genotype data of G-13915 showed remarkable deviation from the HWE which can be attributed to both inbreeding and selective pressure.
Keywords: Lactose intolerance, Adult-Type Hypolactasia (ATH) Lactase Persistence/Non-Persistence, Hydrogen Breath Test, C/T-13910, T/G-13915, Sultanate of Oman.
