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Effect of FTO rs9930506 on obesity and interaction of the gene variants with dietary protein and vitamin E on C-reactive protein levels in multi-ethnic Malaysian adults

Mitra SR, Tan PY, Amini F

J Hum Nutr Diet, 2018 12;31(6):758-772.
PMID: 30141234 DOI: 10.1111/jhn.12593

BACKGROUND: Individual variations of obesity-related traits can be a consequence of dietary influence on gene variants.
METHODS: This cross-sectional study aimed to evaluate (i) the effect of FTO rs9930506 on obesity and related parameters and (ii) the influence of diet on the above association in Malaysian adults. In total, 79 obese and 99 nonobese Malaysian adults were recruited.
RESULTS: In comparison with Chinese and Malays, Indians had significantly higher waist circumference (P ≤ 0.001 and P = 0.016), waist-hip ratio (P = 0.001 and P < 0.001), body fat percentage (P = 0.001 and P = 0.042), fasting insulin (P = 0.001 and P = 0.001), homeostatic model assessment-insulin resistance (P = 0.001 and P = 0.001) and lower high-density lipoprotein-cholesterol levels (P < 0.001 and P < 0.001), respectively. Indians consumed significantly lower dietary cholesterol (P = 0.002), percentage energy from protein (P < 0.001) and higher fibre (P = 0.006) compared to the other two groups. Malaysian Indians expressed the highest risk allele frequency (G) of FTO rs9930506 compared to the Malays and the Chinese (P < 0.001). No significant association was found between FTO rs9930506 and obesity (dominant model). Risk allele carriers (G) consumed significantly lower vitamin E (P = 0.020) and had a higher fibre intake (P = 0.034) compared to the noncarriers (A). Gene-diet interaction analysis revealed that risk allele carriers (G) had lower high sensitivity C-reactive protein (hsCRP) levels with higher energy from protein (≥14% day-1 ; P = 0.049) and higher vitamin E (≥5.4 mg day-1 ; P = 0.038).
CONCLUSIONS: The presence of the risk allele (G) of FTO rs9930506 was not associated with an increased risk of obesity. Malaysian Indians had a significantly higher frequency of the risk allele (G). Indian participants expressed higher atherogenic phenotypes compared to Chinese and Malays. FTO rs9930506 may interact with dietary protein and vitamin E and modulate hsCRP levels.

Matched MeSH terms: Gene Frequency
Fulltext Predictive SNPs for β0-thalassemia/HbE disease severity

Munkongdee T, Tongsima S, Ngamphiw C, Wangkumhang P, Peerapittayamongkol C, Hashim HB, et al.

Sci Rep, 2021 05 14;11(1):10352.
PMID: 33990643 DOI: 10.1038/s41598-021-89641-2

β-Thalassemia/HbE disease has a wide spectrum of clinical phenotypes ranging from asymptomatic to dependent on regular blood transfusions. Ability to predict disease severity is helpful for clinical management and treatment decision making. A thalassemia severity score has been developed from Mediterranean β-thalassemia patients. However, different ethnic groups may have different allele frequency and linkage disequilibrium structures. Here, Thai β0-thalassemia/HbE disease genome-wild association studies (GWAS) data of 487 patients were analyzed by SNP interaction prioritization algorithm, interacting Loci (iLoci), to find predictive SNPs for disease severity. Three SNPs from two SNP interaction pairs associated with disease severity were identifies. The three-SNP disease severity risk score composed of rs766432 in BCL11A, rs9399137 in HBS1L-MYB and rs72872548 in HBE1 showed more than 85% specificity and 75% accuracy. The three-SNP predictive score was then validated in two independent cohorts of Thai and Malaysian β0-thalassemia/HbE patients with comparable specificity and accuracy. The SNP risk score could be used for prediction of clinical severity for Southeast Asia β0-thalassemia/HbE population.

Matched MeSH terms: Gene Frequency
Fulltext The haptoglobin 2-2 genotype is associated with inflammation and carotid artery intima-media thickness

Dalan R, Liew H, Goh LL, Gao X, Chew DE, Boehm BO, et al.

Diab Vasc Dis Res, 2016 09;13(5):373-6.
PMID: 27190085 DOI: 10.1177/1479164116645247

The haptoglobin 2-2 genotype is associated with atherosclerosis in type 2 diabetes mellitus. We examined the associations of the haptoglobin 2-2 genotype with C-reactive protein (high-sensitivity C-reactive protein) and carotid artery intima-media thickness, adjusting for age, gender, ethnicity, type 2 diabetes mellitus, smoking status, body mass index, blood pressure, glycated haemoglobin, non-high-density lipoprotein cholesterol and medications via logistic multivariate regression in 200 subjects (160 type 2 diabetes mellitus versus 40 healthy individuals). The prevalence of the haptoglobin 2-2 genotype was 58% (115/200), higher in the Indians than in Chinese (72% versus 45%, p = 0.001). Multivariate analysis showed that the haptoglobin 2-2 genotype was associated with high-sensitivity C-reactive protein [mean: 3.5 ± 3.9 versus 2.2 ± 2.6 mg/L (non-haptoglobin 2-2), p

Matched MeSH terms: Gene Frequency
Clinical significance of SLC2A9/GLUT9 rs11722228 polymorphisms in gout

Das Gupta E, Sakthiswary R, Lee SL, Wong SF, Hussein H, Gun SC

Int J Rheum Dis, 2018 Mar;21(3):705-709.
PMID: 27456670 DOI: 10.1111/1756-185X.12918

AIM: The main objective of this study is to elucidate the clinical significance of the SLC2A9/GLUT9 rs11722228 polymorphism among male gout patients.
METHOD: We consecutively recruited all newly diagnosed male gout patients who were treatment-naive from the rheumatology outpatient clinics of two Malaysian hospitals. Age-matched healthy male adults were employed as controls. All subjects were tested for the SLC2A9/GLUT9 rs11722228 genotypes, serum uric acid (SUA), urine uric acid and creatinine levels. All gout subjects were examined for the presence of tophi and sonographically screened for renal calculi.
RESULTS: A total of 73 male gout patients and 73 age-matched healthy male adults were recruited in this study. The genotypic frequencies of SLC2A9/GLUT9 rs1172228 did not differ significantly between the gout cases and the healthy controls. The gout subjects with the CC genotype had significantly higher SUA levels (P = 0.002), family history of gout (P < 0.050) and the occurrence of renal calculi (P = 0.026). The SUA-adjusted odds ratios (OR) of the occurrence of renal calculi in the CC genotype (OR = 1 [reference]) was significantly higher than the CT genotype (OR = 0.338, 95%CI: 0.141-0.813) and the TT genotype (OR = 0.271, 95%CI: 0.086-0.854).
CONCLUSIONS: The genotypic distribution of SLC2A9/GLUT9 rs1172228 in male gout patients did not differ significantly from that of healthy male controls. However, the CC genotype in gout had significant associations with higher levels of SUA, renal calculi and a positive family history of gout.
Study site: Rheumatology clinic, Tuanku Jaafar Hospital, Malaysia and Putrajaya Hospital, Malaysia

Matched MeSH terms: Gene Frequency
Fulltext Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer

Hampras SS, Sucheston-Campbell LE, Cannioto R, Chang-Claude J, Modugno F, Dörk T, et al.

Oncotarget, 2016 10 25;7(43):69097-69110.
PMID: 27533245 DOI: 10.18632/oncotarget.10215

BACKGROUND: Regulatory T (Treg) cells, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and, thus, variants in genes encoding Treg cell immune molecules could be associated with ovarian cancer.
METHODS: In a population of 15,596 epithelial ovarian cancer (EOC) cases and 23,236 controls, we measured genetic associations of 1,351 SNPs in Treg cell pathway genes with odds of ovarian cancer and tested pathway and gene-level associations, overall and by histotype, for the 25 genes, using the admixture likelihood (AML) method. The most significant single SNP associations were tested for correlation with expression levels in 44 ovarian cancer patients.
RESULTS: The most significant global associations for all genes in the pathway were seen in endometrioid ( p = 0.082) and clear cell ( p = 0.083), with the most significant gene level association seen with TGFBR2 ( p = 0.001) and clear cell EOC. Gene associations with histotypes at p < 0.05 included: IL12 ( p = 0.005 and p = 0.008, serous and high-grade serous, respectively), IL8RA ( p = 0.035, endometrioid and mucinous), LGALS1 ( p = 0.03, mucinous), STAT5B ( p = 0.022, clear cell), TGFBR1 ( p = 0.021 endometrioid) and TGFBR2 ( p = 0.017 and p = 0.025, endometrioid and mucinous, respectively).
CONCLUSIONS: Common inherited gene variation in Treg cell pathways shows some evidence of germline genetic contribution to odds of EOC that varies by histologic subtype and may be associated with mRNA expression of immune-complex receptor in EOC patients.

Matched MeSH terms: Gene Frequency
PXR, CAR and HNF4alpha genotypes and their association with pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin in Asian patients

Hor SY, Lee SC, Wong CI, Lim YW, Lim RC, Wang LZ, et al.

Pharmacogenomics J, 2008 Apr;8(2):139-46.
PMID: 17876342

Previously studied candidate genes have failed to account for inter-individual variability of docetaxel and doxorubicin disposition and effects. We genotyped the transcriptional regulators of CYP3A and ABCB1 in 101 breast cancer patients from 3 Asian ethnic groups, that is, Chinese, Malays and Indians, in correlation with the pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin. While there was no ethnic difference in docetaxel and doxorubicin pharmacokinetics, ethnic difference in docetaxel- (ANOVA, P=0.001) and doxorubicin-induced (ANOVA, P=0.003) leukocyte suppression was observed, with Chinese and Indians experiencing greater degree of docetaxel-induced myelosuppression than Malays (Bonferroni, P=0.002, P=0.042), and Chinese experiencing greater degree of doxorubicin-induced myelosuppression than Malays and Indians (post hoc Bonferroni, P=0.024 and 0.025). Genotyping revealed both PXR and CAR to be well conserved; only a PXR 5'-untranslated region polymorphism (-24381A>C) and a silent CAR variant (Pro180Pro) were found at allele frequencies of 26 and 53%, respectively. Two non-synonymous variants were identified in HNF4alpha (Met49Val and Thr130Ile) at allele frequencies of 55 and 1%, respectively, with the Met49Val variant associated with slower neutrophil recovery in docetaxel-treated patients (ANOVA, P=0.046). Interactions were observed between HNF4alpha Met49Val and CAR Pro180Pro, with patients who were wild type for both variants experiencing least docetaxel-induced neutropenia (ANOVA, P=0.030). No other significant genotypic associations with pharmacokinetics or pharmacodynamics of either drug were found. The PXR-24381A>C variants were significantly more common in Indians compared to Chinese or Malays (32/18/21%, P=0.035) Inter-individual and inter-ethnic variations of docetaxel and doxorubicin pharmacokinetics or pharmacodynamics exist, but genotypic variability of the transcriptional regulators PAR, CAR and HNF4alpha cannot account for this variability.

Matched MeSH terms: Gene Frequency
Current trends in morbidity and mortality of children in Malaysia

Lin, Hai Peng, Mohd Sham Kasim

Malaysian Journal of Child Health, 1997;9(2):104-132.
MyJurnal

Malaysia is a rapidly developing country with a very young population, about 36% of which are below the age of 15 years. The standard of child health has improved greatly. However, there are great changes in the morbidity and mortality patterns of childhood diseases relating mainly to an improved standard of living; availability of safe water supply and adequate sanitary latrines; a higher literacy rate; rapid industrialisation and urban migration. The infant mortality rate has droppedfrom 50.1 per 1,000 livebirths in 1986 to 10.4 in 1995, and similar trends apply also to neonatal, perinatal and toddler mortality rates. Nevertheless, current major child health problems are those relating to events in the perinatal period and to infections. Despite improvements in the standard of neonatal care with the use ofhigh technology, the commonest cause of certified deaths still occur in the neonatal period. A rapid and inexpensive screening test for G6PD deficiency, a disease present in 2-3% of the population, is now widely available and, together with the use of phototherapy is largely responsible for the declining incidence of kernicterus in the country. Infections remain an important cause of morbidity and mortality although their patterns have changed. The very high (>95%) WHO-EPI-vaccines coverage rate is linked to the great reduction in the incidence of diphtheria, pertussis, tetanus, poliomyelitis and measles. Childhood tuberculosis is less common now, with about 250 - 300 reported cases per year and TB meningitis is rare with about 30-40 reported cases/year. The hepatitis B carrier rate is high (5%) and the introduction of routine newborn hepatitis B vaccination in 1989 is expected to have a positive impact as is the immunisation of young girls against rubella introduced in 1985 in reducing the incidence of congenital rubella syndrome. The incidence of malaria has declined but remains prevalent in the interiors of PeninsularMalaysia and in Sabah and Sarawak. Filariasis is largely under control. Unfortunately, despite great efforts at mosquito control, dengue virus infection remains a major problem with thousands of cases reported every year. Children are most susceptible to dengue haemorrhagic fever with many dying from the shock syndrome. The incidence of acute gastroenteritis has also dropped with most cases being due to a viral aetiology. Acute respiratory infections, mostly viral in origin, account for most attendances at paediatric outpatient services. Although staphylococcal and streptococcal impetigo and pneumonia are common, the incidence of streptococcal related diseases like rheumatic fever and acute glomendonephritis is rapidly declining. The nutritional status of children has improved in tandem with the rise in the standard of living, but subclinical malnutrition is prevalent, particularly among urban squatters and the rural poor. There is a disturbing decline in breastfeeding among urban working mothers. Poor weaning practices and food habits are responsible for the common occurrence of nutritional anaemia (5%) among infants and young children. Greater prosperity, rapid industrialisation and urbanisation have resulted in changes in the childhood disease pattern where non-communicable diseases assume greater importance as the problems of malnutrition and infection are gradually overcome. Road traffic accidents are a major killer and home accidents, largely preventable, are an important cause of morbidity and mortality. Childhood cancer, with about 550 new cases a year, is an important cause of death beyond infancy. Major congenital malformations, with a 1% prevalence rate, cause much ill-health. Thalassaemia is a particularly common genetic disease with fl thalassaemia gene frequency of about 5%. The prevalence of asthma is increasing, with a rate of 13.9% in the Kiang Valley but the prevalence of asthma-related symptoms is much higher. Physical, sexual child abuse and neglect, abandoned babies, substance abuse are but signs of stress of modern city living and peoples inability to cope with it. Although the general standard of child health has greatly improved, there are several states where it is still not satisfactory. In Sabah where there is a large illegal immigrant population, the infant mortality and infection rates are relatively high. In Kelantan and Trengganu, it is common for parents to refuse permission for a lumbar puncture required to treat meningitis. Other still deeply entrenched, culturally-related adverse health practices include : a fatalistic attitude to illness; a preference for traditional practitioners of medicine resulting in late treatment; and 'doctor-hopping' with unrealistic expectations of 'instant cure'. Childhood illnesses that are uncommon in Malaysia include: cystic fibrosis, coeliac disease, ulcerative colitis, Crohns disease, Sudden Infant Death Syndrome, Encopresis, enuresis and epiglottitis due to Haemophilus Influen:ae.

Matched MeSH terms: Gene Frequency