Study on influence of age, gender and genetic variants on lactose intolerance and its impact on milk intake in adult Asian Indians.

BACKGROUND: Lactase non-persistence (LNP) has been associated with the CC genotype of -13910C > T and GG genotype of -22018G > A polymorphisms present upstream of the lactase gene. Lactose intolerance (LI) is caused when gastrointestinal symptoms develop in individuals with low lactase activity. OBJECTIVE: To analyse association of LNP genotype and LI symptoms with milk intake and determine whether factors such as age, gender and genotype affect LI status. SUBJECTS AND METHODS: Genetic analysis and lactose tolerance test (LTT) were performed on 205 healthy Indian adults. The pattern of milk consumption was recorded using a dietary questionnaire. RESULTS: LI was strongly associated with -13910CC genotype (OR = 10.28, 95% CI = 2.32-45.55, p = 0.002). Females were found to be at a higher risk of developing LI (OR = 2.47, 95% CI = 1.33-4.59, p = 0.004). The association of the ≥50 years age group with LI was marginally significant (OR = 1.86, 95% CI = 0.995-3.47, p = 0.05). Frequency and quantity of milk intake were lower in subjects belonging to the LNP genotype and LI groups (p < 0.05). CONCLUSIONS: Subject study suggests that gender and genotype may be associated with development of LI. Association of age with LI was marginal. The data also indicate that LNP genotype and LI may play a role in influencing milk intake in individuals.

Association of paraoxonase1 gene Q192R polymorphism and apolipoprotein B in Asian Indian women with coronary artery disease risk.

BACKGROUND/AIMS: Human serum paraoxonase1 (PON1), a high-density lipoprotein-associated enzyme, prevents oxidative modification of low-density lipoprotein and, thus, arrests the development of atheroma formation, whose major consequence is the development of coronary artery disease (CAD). A single-nucleotide polymorphism (SNP) Q192R in the coding region at pon1 locus is a determinant of PON1 activity. The relationship between PON1 activity and vascular disease may be influenced by the relationship of PON1 activity or PON1 SNP genotype to lipid and apolipoprotein (Apo) levels. The aim of the study is to ascertain the prevalence of PON1 Q192R polymorphism in male and female subjects with and without CAD along with its influence on ApoA-I and ApoB levels in Asian Indians. METHODS: Determination of genotypes was carried out in 249 diagnosed CAD cases and in 243 age-, gender-matched asymptomatic controls by polymerase chain reaction-restriction fragment length polymorphism. Fasting plasma Apo-levels were estimated by immunoturbidimetric assay. RESULTS: The genotype frequencies did not differ markedly between the overall CAD and control groups and in male and female subjects, suggesting a lack of any genotype-CAD correlation. ApoB levels were found to be higher in female patients carrying RR when compared with QQ genotypes (p=0.03) with no effect on controls. This may be attributed to the postmenopausal state of the women. CONCLUSION: PON1 Q192R can be used as the DNA marker test to evaluate the risk of CAD in postmenopausal Indian women with high ApoB.

Full-gene-sequencing analysis of N-acetyltransferase-2 in an adult Indian population.

AIMS: Drug-metabolizing enzymes play a major role in determining the outcome of drug therapy. N-acetyltransferase-2 (NAT2) is one of the main enzymes involved in metabolism of isoniazid used in treatment of tuberculosis (TB). Several variations in the NAT2 gene give rise to multiple haplotypes that phenotypically code for different acetylator status. The objective was to generate a more unambiguous picture of the NAT2 scenario in India as compared to that obtained from polymerase chain reaction-restriction fragment length polymorphism methods. METHODS: Full-gene-sequencing analysis of NAT2 was carried out in 181 healthy Indian subjects from different regional groups. RESULTS: A total of 33 diplotypes were recorded from six known single-nucleotide polymorphisms. The overall frequency of the slow acetylator haplotypes detected in this study was 65%, followed by 26% and 9% intermediate and rapid acetylators, respectively. Of the slow acetylator alleles, the NAT2*5B/*6A occurred in 25% of the study subjects. CONCLUSIONS: The study indicates that the frequency of slow acetylator alleles is high in the adult Indian population. Since the prevalence of TB is high in this population, pharmacogenetic testing for NAT2 alleles may be advisable before start of therapy with isoniazid to prevent drug toxicity.

A study on genetic test of lactase persistence in relation to milk consumption in regional groups of India.

BACKGROUND: Lactase nonpersistence (LNP) is characterized by the decrease in lactase expression in the small intestine. Studies have shown that -13910 C>T and -22018 G>A single-nucleotide polymorphisms (SNPs) located upstream of the lactase gene are associated with an LNP/lactase persistence (LP) trait. OBJECTIVE: The current study evaluated the LP allelic frequency in 227 healthy Indian subjects consisting of North Indians, Maharashtrians, Gujaratis, Parsis, and South Indians, and for the first time assessed its relation with milk consumption pattern in Indian subjects. METHODS: The two SNPs were genotyped using the polymerase chain reaction and restriction fragment length polymorphism methods. The milk consumption pattern for the studied subjects was noted by questionnaire. RESULTS: The two SNPs were present in a strong linkage disequilibrium. LP prevalence varied in these Indian regional groups. The LP frequency was highest for North Indians and lowest for Parsis (p=0.03 CC vs. CT+TT, p=0.008 GG vs. GA+AA). South Indians had a lower LP frequency compared to North Indians (p=0.07 for each SNP). The milk consumption pattern varied in these Indian subgroups, with the Gujaratis exhibiting the highest milk intake and Parsis the lowest (p=0.04). CONCLUSION: Our study indicates that the milk intake in Indians might be influenced by their dietary habits in addition to their ancestral history. An overall correlation, however, between milk consumption and LP genotypes was not observed.

Genotype frequencies of drug-metabolizing enzymes responsible for purine and pyrimidine antagonists in a healthy Asian-Indian population.

Purine and pyrimidine antimetabolites are used to treat leukemias, autoimmune diseases, and solid tumors. Detection of slow metabolizers before administration of the drugs is necessary to prevent any subsequent drug toxicity. With this aim, we determined the frequencies of normal and slow alleles in our population. Polymorphisms in genes encoding cytidine deaminase (CDA), dihydropyrimidine dehydrogenase (DPYD), and thiopurine-S-methyltransferase (TPMT) were documented in 225 healthy volunteers. The polymorphisms typed included CDA*3, DPYD*2A, TPMT*2A, TPMT*3B, and TPMT*3C. Methods used for genotyping included standard PCR-RFLP and allele-specific PCR reactions. The frequencies were 0.44 % for DPYD*2A, 0.67 % for TPMT*3B, and 0.89 % for TPMT*3C. The CDA*3 and TPMT*2A alleles were not detected. Although these polymorphisms have been demonstrated to be associated with drug toxicity in other populations, they appear to be very rare in the adult Indian population.

Gene polymorphisms and low dietary intake of micronutrients in coronary artery disease.

BACKGROUND/AIMS: Coronary artery disease (CAD) is a complex disorder involving genetic and non-genetic factors. Food is an important component of the latter. We examined if DNA polymorphisms in genes encoding enzymes of one-carbon metabolism coupled with low consumption of micronutrients such as folate, vitamins B(6) and B(12) might increase the risk of CAD. METHODS: A case-control study consisting of 252 CAD patients and 252 controls were included. Three single nucleotide polymorphisms (SNP), 2 insertion/deletion and 1 repeat polymorphism were typed. The micronutrient intake was estimated from a standard 24-hour dietary recall coupled to a food frequency questionnaire. RESULTS: The results suggest an association of 'early-onset CAD' with betaine homocysteine S-methyl transferase (BHMT) 742G→A SNP (odds ratio = 1.52; 95% confidence interval, 0.96-2.41; p = 0.04). No association was observed for all age of onset, but more patients than controls whose micronutrient intake was in the lowest quintile also carried the minor allele (50% patients vs. 37% controls; p = 0.042). Furthermore, dietary intake of folate micronutrients below the recommended daily allowance was observed in a larger percent of patients than controls with the minor BHMT allele (51% patients vs. 44% controls; p = 0.021). CONCLUSIONS: In the presence of the minor BHMT allele, a decreased consumption of folate micronutrients might increase the risk of CAD.